Fibroblasts In Inflammation Research Articles

Antagonistic effects of activin A and TNF-\u03b1 on the activation of L929 fibroblast cells via Smad3-independent signaling

Fibroblasts play an important role in inflammation and tissue fibrosis. Both activin A and TNF-α can activate immune cells, however, the roles and relationship of them in activating fibroblasts in inflammation remain unclear. Here, this study revealed that TNF-α promoted the release of NO and IL-6 by L929 fibroblast cells, but co-treatment with activin A attenuated these effects. In contrast, activin A induced cell migration and increased the production of tissue fibrosis-related TGF-β1 and fibronectin, while TNF-α inhibited these function changes of L929 cells induced by activin A. Moreover, this study revealed that activin A and TNF-α regulated the activities of L929 cells via ERK1/2/MAPK pathway, rather than Smad3-dependent signaling pathway. Taken together, these data indicate that activin A and TNF-α exert mutually antagonistic effects on regulating fibroblasts activities, and the balance between their action may determine the process and outcome of fibroblasts-mediated inflammation.

Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma

In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to controls. IL-1α/β induced fibroblast pro-inflammatory responses (CXCL8/IL-8, IL-6, TSLP, GM-CSF) and suppressed ECM-production (collagen, fibronectin, periostin) and the cell’s ability to repair and remodel fibrillar collagen I via LOX, LOXL1 and LOXL2 activity, as confirmed by inhibition with β-aminopropionitrile. These data support a role for epithelial-derived-IL-1 in the dysregulated repair of the asthmatic-EMTU and provides new insights into the contribution of airway fibroblasts in inflammation and airway remodeling in asthma.

Modeled Osteopathic Manipulative Treatments: A Review of Their in Vitro Effects on Fibroblast Tissue Preparations.

A key osteopathic tenet involves the body's ability to self-heal. Osteopathic manipulative treatment (OMT) has been evolved to improve this healing capacity. The authors' in vitro work has focused on modeling 2 common OMT modalities: myofascial release (MFR) and counterstrain. Their studies have evaluated the effects of these modalities on wound healing, cytokine secretion, and muscle repair. The key components of the host response to mechanical forces are fibroblasts, which are the main fascial cells that respond to different types of strain by secreting anti-inflammatory chemicals and growth factors, thus improving wound healing and muscle repair processes. The purpose of this review is to discuss the cellular and molecular mechanisms by which MFR and other OMT modalities work, in particular, the role of strained fibroblasts in inflammation, wound healing, and muscle repair and regeneration. Changing MFR parameters, such as magnitude, duration, direction, and frequency of strain, might uniquely affect the physiologic response of fibroblasts, muscle contraction, and wound healing. If such results are clinically translatable, the mechanisms underlying the clinical outcomes of OMT modalities will be better understood, and these treatments will be more widely accepted as evidence-based, first-line therapies.

Role of intestinal fibroblasts in inflammation across the intestinal epithelium (488.10)

Fibroblasts are mesenchymal cells that produce extracellular matrix (ECM) proteins and play a major role in tissue repair (i.e., resolution of inflammation). Fibroblasts can affect cells in the local environment through the release of cytokines, growth and differentiation factors. CD36 is a membrane‐bound and scavenger receptor that is an indicator of inflammation and interacts with TLR‐2, 4, and 6. We investigated intestinal fibroblasts for expression of immune receptors and for a role of CD36 in intestinal inflammation using fibroblasts exposed to a series of cytokines. Analysis of supernatants revealed the presence of IL‐8 (potent chemoattractant for polymorphonuclear leukocytes, (PMN)) in IL‐6 treated normal and CD36‐deficient fibroblasts. However, results reveal a statistically significant reduction in PMN migration using IL‐6 treated CD36‐deficient cells. Kinase inhibitor experiments reveal that PI3 kinase pathway may be involved in the lL‐6 mediated release of IL‐8 from fibroblasts. Fibroblasts exposed to IL‐8 have been reported to display a myofibroblast‐like phenotype. Differences in cell adhesion and migration were also revealed using CD36‐deficient fibroblasts. Results show that fibroblasts can play a major role in the inflammatory responses in the intestine, PI3 kinase may be involved, and highlight CD36 as a target‐receptor that may modulate the inflammatory responses of fibroblasts.Grant Funding Source: NSF‐RII, NIH/NIDDK 5T35 DK007431

The role of stromal cells in the persistence of chronic inflammation.

Inflammation is an unstable state; it either resolves or persists. Inflammatory reactions often have a propensity for specific anatomical sites. Why inflammation persists with specific tissue tropism remains obscure. Increasing evidence suggests that stromal cells which define tissue architecture are the key cells involved, and therefore make attractive therapeutic targets. Research on stromal cells in general and fibroblasts in particular has so far been hampered by a lack of fibroblast-specific cell markers. This review highlights our increasing understanding of the role of fibroblasts in inflammation, and suggests that these cells provide the cellular basis for site specific chronic inflammation.