The Experts below are selected from a list of 9466647 Experts worldwide ranked by ideXlab platform
Thirumala-devi Kanneganti - One of the best experts on this subject based on the ideXlab platform.
-
gasdermin d promotes AIM2 inflammasome activation and is required for host protection against francisella novicida
Journal of Immunology, 2018Co-Authors: Qifan Zhu, Rajendra Karki, Min Zheng, Arjun Balakrishnan, Thirumala-devi KannegantiAbstract:The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida –infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.
-
detrimental type i interferon signaling dominates protective AIM2 inflammasome responses during francisella novicida infection
Cell Reports, 2018Co-Authors: Qifan Zhu, Si Ming Man, Rajendra Karki, R.k. Subbarao Malireddi, Thirumala-devi KannegantiAbstract:Summary Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida . Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses.
-
brucella abortus triggers a cgas independent sting pathway to induce host protection that involves guanylate binding proteins and inflammasome activation
Journal of Immunology, 2018Co-Authors: Miriam Costa M Franco, Fernanda Martins Marim, Erika S Guimaraes, Natan R G Assis, Daiane M Cerqueira, Juliana Alvessilva, Jerome S Harms, Gary A Splitter, Judith A Smith, Thirumala-devi KannegantiAbstract:Immunity against microbes depends on recognition of pathogen-associated molecular patterns by innate receptors. Signaling pathways triggered by Brucella abortus DNA involves TLR9, AIM2, and stimulator of IFN genes (STING). In this study, we observed by microarray analysis that several type I IFN–associated genes, such as IFN-β and guanylate-binding proteins (GBPs), are downregulated in STING knockout (KO) macrophages infected with Brucella or transfected with DNA. Additionally, we determined that STING and cyclic GMP–AMP synthase (cGAS) are important to engage the type I IFN pathway, but only STING is required to induce IL-1β secretion, caspase-1 activation, and GBP2 and GBP3 expression. Furthermore, we determined that STING but not cGAS is critical for host protection against Brucella infection in macrophages and in vivo. This study provides evidence of a cGAS-independent mechanism of STING-mediated protection against an intracellular bacterial infection. Additionally, infected IFN regulatory factor-1 and IFNAR KO macrophages had reduced GBP2 and GBP3 expression and these cells were more permissive to Brucella replication compared with wild-type control macrophages. Because GBPs are critical to target vacuolar bacteria, we determined whether GBP2 and GBP chr3 affect Brucella control in vivo. GBP chr3 but not GBP2 KO mice were more susceptible to bacterial infection, and small interfering RNA treated–macrophages showed reduction in IL-1β secretion and caspase-1 activation. Finally, we also demonstrated that Brucella DNA colocalizes with AIM2, and AIM2 KO mice are less resistant to B. abortus infection. In conclusion, these findings suggest that the STING-dependent type I IFN pathway is critical for the GBP-mediated release of Brucella DNA into the cytosol and subsequent activation of AIM2.
-
Detrimental Type I Interferon Signaling Dominates Protective AIM2 Inflammasome Responses during Francisella novicida Infection
Elsevier, 2018Co-Authors: Qifan Zhu, Si Ming Man, Rajendra Karki, R.k. Subbarao Malireddi, Thirumala-devi KannegantiAbstract:Summary: Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses. : Zhu et al. show that, although type I IFN signaling is required for activating AIM2 inflammasome in response to Francisella novicida in macrophages, these components have strikingly opposing effects in vivo. Deleterious type I IFN signaling dominates protective AIM2 inflammasome responses by inducing apoptotic cell death. Keywords: inflammasomes, AIM2, caspase-3, caspase-7, caspase-8, apoptosis, TRAIL, Francisella novicida, interferon, innate immunit
-
priming and activation of inflammasome by canarypox virus vector alvac via the cgas ifi16 sting type i ifn pathway and AIM2 sensor
Journal of Immunology, 2017Co-Authors: Fengliang Liu, Thirumala-devi Kanneganti, Qingli Niu, Xiuzhen Fan, Connie Liu, Jie Zhang, Zhi Wei, Wei Hou, Merlin L Robb, Jerome H KimAbstract:Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs. Microarray and comprehensive gene-knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome activation. We also provided evidence that, in contrast to ALVAC, the Ad5 vector itself was unable to induce inflammasome activation, which was related to its inability to stimulate the STING-type I IFN pathway and to provide inflammasome-priming signals. In preconditioned APCs, the Ad5 vector could stimulate inflammasome activation through an AIM2-independent mechanism. Therefore, our study identifies the AIM2 inflammasome and cGAS/IFI16-STING-type I IFN pathway as a novel mechanism for host innate immunity to the ALVAC vaccine vector.
Divaker Choubey - One of the best experts on this subject based on the ideXlab platform.
-
distinct regulation of murine lupus susceptibility genes by the irf5 blimp 1 axis
Journal of Immunology, 2012Co-Authors: Ravichandran Panchanathan, Divaker Choubey, Hongzhu Liu, Hongqi Liu, Cheemun Fang, Loren D Erickson, Paula M PithaAbstract:Genome-wide association studies have identified lupus susceptibility genes such as IRF5 and PRDM1 (encoding for IFN regulatory factor 5 [IRF]5 and Blimp-1) in the human genome. Accordingly, the murine Irf5 and Prdm1 genes have been shown to play a role in lupus susceptibility. However, it remains unclear how IRF5 and Blimp-1 (a transcriptional target of IRF5) contribute to lupus susceptibility. Given that the murine lupus susceptibility locus Nba2 includes the IFN-regulated genes Ifi202 (encoding for the p202 protein), AIM2 (encoding for the AIM2 protein), and Fcgr2b (encoding for the FcγRIIB receptor), we investigated whether the IRF5/Blimp-1 axis could regulate the expression of these genes. We found that an Irf5 deficiency in mice decreased the expression of Blimp-1 and reduced the expression of the Ifi202. However, the deficiency increased the expression of AIM2 and Fcgr2b. Correspondingly, increased expression of IRF5 in cells increased levels of Blimp-1 and p202 protein. Moreover, Blimp-1 expression increased the expression of Ifi202, whereas it reduced the expression of AIM2. Interestingly, an AIM2 deficiency in female mice increased the expression of IRF5. Similarly, the Fcgr2b-deficient mice expressed increased levels of IRF5. Moreover, increased expression of IRF5 and Blimp-1 in lupus-prone C57BL/6.Nba2, New Zealand Black, and C57BL/6.Sle123 female mice (as compared with age-matched C57BL/6 female mice) was associated with increased levels of the p202 protein. Taken together, our observations demonstrate that the IRF5/Blimp-1 axis differentially regulates the expression of Nba2 lupus susceptibility genes, and they suggest an important role for the IRF5/Blimp-1/p202 axis in murine lupus susceptibility.
-
Interferon-inducible p200-family protein IFI16, an innate immune sensor for cytosolic and nuclear double-stranded DNA: regulation of subcellular localization.
Molecular Immunology, 2011Co-Authors: Sudhakar Veeranki, Divaker ChoubeyAbstract:Abstract The interferon (IFN)-inducible p200-protein family includes structurally related murine (for example, p202a, p202b, p204, and AIM2) and human (for example, AIM2 and IFI16) proteins. All proteins in the family share a partially conserved repeat of 200-amino acid residues (also called HIN-200 domain) in the C-terminus. Additionally, most proteins (except the p202a and p202b proteins) also share a protein–protein interaction pyrin domain (PYD) in the N-terminus. The HIN-200 domain contains two consecutive oligosaccharide/oligonucleotide binding folds (OB-folds) to bind double stranded DNA (dsDNA). The PYD domain in proteins allows interactions with the family members and an adaptor protein ASC. Upon sensing cytosolic dsDNA, AIM2, p204, and AIM2 proteins recruit ASC protein to form an inflammasome, resulting in increased production of proinflammatory cytokines. However, IFI16 protein can sense cytosolic as well as nuclear dsDNA. Interestingly, the IFI16 protein contains a nuclear localization signal (NLS). Accordingly, the initial studies had indicated that the endogenous IFI16 protein is detected in the nucleus and within the nucleus in the nucleolus. However, several recent reports suggest that subcellular localization of IFI16 protein in nuclear versus cytoplasmic (or both) compartment depends on cell type. Given that the IFI16 protein can sense cytosolic as well as nuclear dsDNA and can initiate different innate immune responses (production of IFN-β versus proinflammatory cytokines), here we evaluate the experimental evidence for the regulation of subcellular localization of IFI16 protein in various cell types. We conclude that further studies are needed to understand the molecular mechanisms that regulate the subcellular localization of IFI16 protein.
-
interferon inducible p200 family proteins as novel sensors of cytoplasmic dna role in inflammation and autoimmunity
Journal of Interferon and Cytokine Research, 2010Co-Authors: Divaker Choubey, Xin Duan, Eric Dickerson, Larissa V Ponomareva, Ravichandran Panchanathan, Hui Shen, Ratika SrivastavaAbstract:Deregulated innate immune responses that result in increased levels of type I interferons (IFNs) and stimulation of IFN-inducible genes are thought to contribute to chronic inflammation and autoimmunity. One family of IFN-inducible genes is the Ifi200 family, which includes the murine (eg, Ifi202a, Ifi202b, Ifi203, Ifi204, Mndal, and AIM2) and human (eg, IFI16, MNDA, IFIX, and AIM2) genes. Genes in the family encode structurally related proteins (the p200-family proteins), which share at least one partially conserved repeat of 200-amino acid (200-AA) residues. Consistent with the presence of 2 consecutive oligonucleotide/oligosaccharide-binding folds in the repeat, the p200-family proteins can bind to DNA. Additionally, these proteins (except the p202 proteins) also contain a pyrin (PYD) domain in the N-terminus. Increased expression of p202 proteins in certain strains of female mice is associated with lupus-like disease. Interestingly, only the AIM2 protein is conserved between the mouse and humans. Several recent studies have provided evidence that the AIM2 and p202 proteins can recognize DNA in cytoplasm and the AIM2 protein upon sensing DNA can form a caspase-1-activating inflammasome. In this review, we discuss how the ability of p200-family proteins to sense cytoplasmic DNA may contribute to the development of chronic inflammation and associated diseases.
-
cytoplasmic localization of the interferon inducible protein that is encoded by the AIM2 absent in melanoma gene from the 200 gene family
FEBS Letters, 2000Co-Authors: Divaker Choubey, Scott Walter, Yanbiao Geng, Hong XinAbstract:While interferons (IFNs) (K, L and Q), a family of cytokines, have the ability to exert the growth-inhibitory effect on target cells, the molecular mechanism(s) by which IFNs inhibit cell growth remains to be identified. Because IFN- inducible 'effector' proteins mediate the biological activities of IFNs, characterization of IFN-inducible proteins is critical to identify their functional role in IFN action. One family (the 200- family) of IFN-inducible proteins is encoded by structurally related murine (Ifi202a, Ifi202b, Ifi203, Ifi204 and D3) and human (IFI16, MNDA and AIM2) genes. The proteins encoded by genes in the family share a unique repeat of 200-amino acids and are primarily nuclear. The AIM2 gene is a newly identified gene that is not expressed in a human melanoma cell line. Here we report that AIM2 is estimated to be a 39 kDa protein and, unlike other proteins in the family, is localized primarily in the cytoplasm. Interestingly, overexpression of AIM2 in transfected cells retards proliferation and, under reduced serum conditions, increases the susceptibility to cell death. Moreover, AIM2 can heterodimerize with p202 in vitro. Together, these observations provide support to the idea that AIM2 may be an important mediator of IFN action. z 2000 Federation of European Biochemical Societies.
Rajendra Karki - One of the best experts on this subject based on the ideXlab platform.
-
gasdermin d promotes AIM2 inflammasome activation and is required for host protection against francisella novicida
Journal of Immunology, 2018Co-Authors: Qifan Zhu, Rajendra Karki, Min Zheng, Arjun Balakrishnan, Thirumala-devi KannegantiAbstract:The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida –infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.
-
detrimental type i interferon signaling dominates protective AIM2 inflammasome responses during francisella novicida infection
Cell Reports, 2018Co-Authors: Qifan Zhu, Si Ming Man, Rajendra Karki, R.k. Subbarao Malireddi, Thirumala-devi KannegantiAbstract:Summary Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida . Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses.
-
Detrimental Type I Interferon Signaling Dominates Protective AIM2 Inflammasome Responses during Francisella novicida Infection
Elsevier, 2018Co-Authors: Qifan Zhu, Si Ming Man, Rajendra Karki, R.k. Subbarao Malireddi, Thirumala-devi KannegantiAbstract:Summary: Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses. : Zhu et al. show that, although type I IFN signaling is required for activating AIM2 inflammasome in response to Francisella novicida in macrophages, these components have strikingly opposing effects in vivo. Deleterious type I IFN signaling dominates protective AIM2 inflammasome responses by inducing apoptotic cell death. Keywords: inflammasomes, AIM2, caspase-3, caspase-7, caspase-8, apoptosis, TRAIL, Francisella novicida, interferon, innate immunit
-
critical role for the dna sensor AIM2 in stem cell proliferation and cancer
Cell, 2015Co-Authors: Si Ming Man, Qifan Zhu, Rajendra Karki, R.k. Subbarao Malireddi, Liqin Zhu, Zhiping Liu, Ankit Malik, Deepika Sharma, Prajwal GurungAbstract:Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that AIM2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in AIM2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of AIM2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer.
-
the transcription factor irf1 and guanylate binding proteins target activation of the AIM2 inflammasome by francisella infection
Nature Immunology, 2015Co-Authors: Rajendra Karki, R.k. Subbarao Malireddi, Geoffrey Neale, Peter Vogel, Masahiro Yamamoto, Mohamed Lamkanfi, Thirumala-devi KannegantiAbstract:The mechanisms that control activation of the AIM2 inflammasome by cytosolic bacteria are unclear. Kanneganti and colleagues demonstrate that a pathway involving the transcription factor IRF1 is required for the activation of AIM2.
Ling Zeng - One of the best experts on this subject based on the ideXlab platform.
-
pkm2 dependent glycolysis promotes nlrp3 and AIM2 inflammasome activation
Nature Communications, 2016Co-Authors: Rui Kang, Timothy R. Billiar, Haichao Wang, Yan Yu, Liangchun Yang, Ling Zeng, Minghua Yang, Jianxin JiangAbstract:Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages. Pharmacological inhibition of the PKM2–EIF2AK2 pathway protects mice from lethal endotoxemia and polymicrobial sepsis. Moreover, conditional knockout of PKM2 in myeloid cells protects mice from septic death induced by NLRP3 and AIM2 inflammasome activation. These findings define an important role of PKM2 in immunometabolism and guide future development of therapeutic strategies to treat sepsis. Inflammation involves a Warburg effect that switches cellular metabolism to glycolysis. Here the authors show this switch drives IL-1β, IL-18 and HMGB1 release from macrophages by activating the NLRP3 and AIM2 inflammasomes via protein kinase R phosphorylation, a pathway that can be inhibited to prevent sepsis in mice.
-
pkm2 dependent glycolysis promotes nlrp3 and AIM2 inflammasome activation
Nature Communications, 2016Co-Authors: Min Xie, Rui Kang, Timothy R. Billiar, Liangchun Yang, Ling Zeng, Minghua Yang, Shan Zhu, Xiaofang Sun, Haichao WangAbstract:Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages. Pharmacological inhibition of the PKM2-EIF2AK2 pathway protects mice from lethal endotoxemia and polymicrobial sepsis. Moreover, conditional knockout of PKM2 in myeloid cells protects mice from septic death induced by NLRP3 and AIM2 inflammasome activation. These findings define an important role of PKM2 in immunometabolism and guide future development of therapeutic strategies to treat sepsis.
Jeffrey S Martin - One of the best experts on this subject based on the ideXlab platform.
-
unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally
PeerJ, 2018Co-Authors: Jeffrey S Martin, Allison M Martin, Petey W Mumford, Lorena P Salom, Angelique N Moore, David D PascoeAbstract:We sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow.Thirty-two participants completed this two-aim study. In AIM1 (n = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m2), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 (n = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m2) involved 30-min unilateral EPC (n = 7) or sham (n = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment.Comparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs; p 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly (p < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points.Unilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies.
-
unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally
PeerJ, 2018Co-Authors: Jeffrey S Martin, Allison M Martin, Petey W Mumford, Lorena P Salom, Angelique N Moore, David D PascoeAbstract:Background We sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow. Methods Thirty-two participants completed this two-aim study. In AIM1 (n = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m2), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 (n = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m2) involved 30-min unilateral EPC (n = 7) or sham (n = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment. Results Comparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs; p 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly (p < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points. Discussion Unilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies.