scholarly journals Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies

2020 ◽  
Author(s):  
Aric Anloague ◽  
Aaron Mahoney ◽  
Oladipupo Ogunbekun ◽  
Taylor Hiland ◽  
William R. Thompson ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Inflammatory Cytokines ◽  
Mechanical Stimulation ◽  
Mechanical Strain ◽  
Dermal Fibroblasts ◽  
Manual Therapies ◽  
Human Dermal Fibroblasts ◽  
Long Duration ◽  
Stimulation Of ◽  
Pro Inflammatory Cytokines

Abstract ObjectiveSoft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. Previous studies established an in vitro model system for examining mechanical stimulation of dermal fibroblasts and established that cyclical strain, intended to mimic overuse injury, induces secretion of numerous pro-inflammatory cytokines. Moreover, mechanical strain intended to mimic soft tissue manual therapy reduces strain-induced secretion of pro-inflammatory cytokines. Here, we sought to partially confirm and extend these reports and provide independent corroboration of prior results.ResultsUsing cultures of primary human dermal fibroblasts, we confirm cyclical mechanical strain increases levels of IL-6 and adding long-duration stretch, intended to mimic therapeutic soft tissue stimulation, after cyclical strain results in lower IL-6 levels. We also extend the prior work, reporting that long-duration stretch results in lower levels of IL-8. Although there are important limitations to this experimental model, these findings provide supportive evidence that therapeutic soft tissue stimulation may reduce levels of pro-inflammatory cytokines. Future work is required to address these open questions and advance the mechanistic understanding of therapeutic soft tissue stimulation.

scholarly journals Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies

2020 ◽  
Author(s):  
Aric Anloague ◽  
Aaron Mahoney ◽  
Oladipupo Ogunbekun ◽  
William R. Thompson ◽  
Bryan Larsen ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Inflammatory Cytokines ◽  
Mechanical Stimulation ◽  
Mechanical Strain ◽  
Dermal Fibroblasts ◽  
Manual Therapies ◽  
Human Dermal Fibroblasts ◽  
Stimulation Of ◽  
Pro Inflammatory Cytokines

Abstract Objective Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. A series of previous studies established an in vitro model system for examining mechanical stimulation of dermal fibroblasts and established that repetitive strain, intended to mimic overuse injury, induces the secretion of numerous pro-inflammatory cytokines. Moreover, mechanical strain intended to mimic soft tissue manual therapy reduces strain-induced secretion of pro-inflammatory cytokines. Here, we sought to partially confirm and extend these reports and provide independent corroboration of prior results. Results Using cultures of primary human dermal fibroblasts, we confirm mechanical forces intended to mimic repetitive motion strain increases levels of IL-6 and that mechanical strain intended to mimic therapeutic soft tissue stimulation reduces IL-6 levels. We also extend the prior work, reporting that therapy-like mechanical stimulation reduces levels of IL-8. Although there are important limitations to this experimental model, these findings provide supportive evidence that therapeutic soft tissue massage may reduce inflammation. Future work is required to address these open questions and advance the mechanistic understanding of therapeutic soft tissue stimulation.

scholarly journals In vitro mimicking of therapeutic soft tissue stimulation regulates pro-inflammatory cytokines

2019 ◽  
Author(s):  
Aric Anloague ◽  
Aaron Mahoney ◽  
Oladipupo Ogunbekun ◽  
William R. Thompson ◽  
Bryan Larsen ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Inflammatory Cytokines ◽  
Mechanical Stimulation ◽  
Soft Tissues ◽  
Physical Therapists ◽  
Mechanical Strain ◽  
Dermal Fibroblasts ◽  
Stimulation Of ◽  
Pro Inflammatory Cytokines

Abstract Objective Soft tissue manual therapies such as massage and myofascial release are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. A series of studies established an in vitro model system for mimicking therapeutic soft tissue stimulation of dermal fibroblasts and established that injury-like strain induces the secretion of numerous pro-inflammatory cytokines. Moreover, mechanical strain replicating soft tissue manual therapy reduces strain-induced secretion of pro-inflammatory cytokines. Here, we sought to partially confirm and extend these reports and provide independent corroboration of prior results. Results Using cultures of primary human dermal fibroblasts, we confirm mechanical force profiles intended to mimic repetitive motion strain increases levels of IL-6 in conditioned media. And, we confirm that mechanical strain intended to mimic therapeutic soft tissue stimulation reduces IL-6 levels. We also extend the prior work, reporting that therapy-like mechanical stimulation reduces levels of IL-8. Collectively, these findings provide supportive evidence that therapeutic soft tissue massage may reduce inflammation. Future work is required to address these open questions and advance the mechanistic understanding of therapeutic mechanical stimulation of soft tissues.

scholarly journals Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

2011 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Linnéa Asp ◽  
Anne-Sofie Johansson ◽  
Amandeep Mann ◽  
Björn Owe-Larsson ◽  
Ewa M Urbanska ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Kynurenine Pathway ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Pro Inflammatory Cytokines

scholarly journals Priming in response to pro-inflammatory cytokines is a feature of adult synovial but not dermal fibroblasts

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Crowley ◽  
John D. O’Neil ◽  
Holly Adams ◽  
Andrew M. Thomas ◽  
Andrew Filer ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Dermal Fibroblasts ◽  
Pro Inflammatory Cytokines

TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP

2001 ◽  
Vol 114 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Y.P. Han ◽  
T.L. Tuan ◽  
H. Wu ◽  
M. Hughes ◽  
W.L. Garner
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Human Skin ◽  
Inflammatory Cytokines ◽  
Intracellular Signaling ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Pro Inflammatory Cytokines

Tumor necrosis factor-alpha (TNF-(alpha)) is an important mediator during the inflammatory phase of wound healing. Excessive amounts of pro-inflammatory cytokines such as TNF-(alpha) are associated with inflammatory diseases including chronic wounds. Matrix metalloproteinases (MMPs) are involved in matrix re-modeling during wound healing, angiogenesis and tumor metastasis. As with pro-inflammatory cytokines, high levels of MMPs have been found in inflammatory states such as chronic wounds. In this report we relate these two phenomena. TNF-(alpha) stimulates secretion of active MMP-2, a type IV collagenase, in organ-cultured full-thickness human skin. This suggests a mechanism whereby excess inflammation affects normal wound healing. To investigate this observation at the cellular and molecular levels, we examined TNF-(alpha) mediated activation of pro-MMP-2, induction of MT1-MMP, and the intracellular signaling pathways that regulate the proteinase in isolated human dermal fibroblasts. We found that TNF-(alpha) substantially promoted activation of pro-MMP-2 in dermal fibroblasts embedded in type-I collagen. In marked contrast, collagen or TNF-(alpha) individually had little influence on the fibroblast-mediated pro-MMP-2 activation. One well-characterized mechanism for pro-MMP-2 activation is through a membrane type matrix metalloproteinase, such as MT1-MMP. We report that TNF-(alpha) significantly induced MT1-MMP at the mRNA and protein levels when the dermal fibroblasts were grown in collagen. Although the intracellular signaling pathway regulating mt1-mmp gene expression is still obscure, both TNF-(alpha) and collagen activate the NF-(kappa)B pathway. In this report we provide three sets of evidence to support a hypothesis that activation of NF-(kappa)B is essential to induce MT1-MMP expression in fibroblasts after TNF-(alpha) exposure. First, SN50, a peptide inhibitor for NF-(kappa)B nuclear translocation, simultaneously blocked the TNF-(alpha) and collagen mediated MT1-MMP induction and pro-MMP-2 activation. Secondly, TNF-(alpha) induced I(kappa)B to breakdown in fibroblasts within the collagen lattice, a critical step leading to NF-(kappa)B activation. Lastly, a consensus binding site for p65 NF-(kappa)B (TGGAGCTTCC) was found in the 5′-flanking region of human mt1-mmp gene. Based on these results and previous reports, we propose a model to explain TNF-(alpha) activation of MMP-2 in human skin. Activation of NF(kappa)B signaling in fibroblasts embedded in collagen induces mt1-mmp gene expression, which subsequently activates the pro-MMP-2. The findings provide a specific mechanism whereby TNF-(alpha) may affect matrix remodeling during wound healing and other physiological and pathological processes.

scholarly journals UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells

2010 ◽  
Vol 206 (2) ◽  
pp. 183-193 ◽  
Author(s):  
José Edgar Nicoletti-Carvalho ◽  
Tatiane C Araújo Nogueira ◽  
Renata Gorjão ◽  
Carla Rodrigues Bromati ◽  
Tatiana S Yamanaka ◽  
...  
Keyword(s):  
Cell Death ◽  
Inflammatory Cytokines ◽  
Interleukin 6 ◽  
Common Mechanism ◽  
Rinm5f Cells ◽  
Β Cell ◽  
Induced Apoptosis ◽  
Unconditional Stimulation ◽  
Stimulation Of ◽  
Pro Inflammatory Cytokines

Unfolded protein response (UPR)-mediated pancreatic β-cell death has been described as a common mechanism by which palmitate (PA) and pro-inflammatory cytokines contribute to the development of diabetes. There are evidences that interleukin 6 (IL6) has a protective action against β-cell death induced by pro-inflammatory cytokines; the effects of IL6 on PA-induced apoptosis have not been investigated yet. In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. In contrast to PA, IL6 efficiently reduced apoptosis induced by pro-inflammatory cytokines. In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2α kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. These findings suggest that IL6 is unable to protect pancreatic β-cells from PA-induced apoptosis because it does not repress UPR activation. In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT.

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