CD40 Expression by human fibroblasts

Fries, Kristin M.; Sempowski, Gregory D.; Gaspari, Anthony A.; Blieden, Timothy M.; Looney, R. John; Phipps, Richard P.

doi:10.1016/0090-1229(95)90135-3

Cited by 152 publications

(137 citation statements)

References 41 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…Fries et al demonstrated that CD40 protein is constitutively expressed on the cell surface of various fibroblast lines derived from lung (from neonates and patients with lung cancer), dermal (from neonates), periodontal (from patients undergoing periodontal surgery), and synovial (from patients with rheumatoid arthritis and osteoarthritis) tissue [18]. Conversely, another report using human gingival fibroblasts showed that engagement by CD154 after the induction of CD40 by IFN-+ on gingival fibroblasts results in an increased production of IL-6 and IL-8, but that the addition of CD154 without pretreatment with IFN-+ has no effect on cytokine production [20].…”

Section: Discussionmentioning

confidence: 99%

“…The CD40-CD154 system is involved in B cell-T cell signaling events and has also been found to be important in nonhematopoietic cell activation. Recently, CD40 has been found on fibroblasts activated by several cytokines [17,18]. Moreover, engagement of CD40 on fibroblasts results in cell proliferation and up-regulation of the proinflammatory cytokines [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40‐CD154 in the phenotype of SSc fibroblasts

et al. 2003

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology that is characterized by tissue fibrosis, which may result from the activation of lesional fibroblasts exhibiting excessive production of extracellular matrix components. However, it has yet to be determined how SSc fibroblasts are activated. CD40 is a cell surface molecule expressed on various cells that is important for the response to activated T cells through CD154. CD40 mRNA was found to be constitutively expressed in both SSc and normal fibroblasts by reverse transcription PCR. Expression of CD40 protein was increased on SSc fibroblasts compared to normal fibroblasts as measured by flow cytometry. Ligation of CD40 by recombinant human CD154 (0.5–2 μg/ml) resulted in increased production of IL‐6, IL‐8, and monocyte chemoattractant protein‐1 in SSc fibroblasts in a dose‐dependent manner, whereas these phenomena were not shown in normal fibroblasts even with the addition of CD154. CD80, a costimulatory molecule, was also induced on SSc fibroblasts by CD40 ligation. In the present study, our findings suggest the possibility of a cell‐mediated response between fibroblasts and T cells in the lesional skin of SSc patients. Since it is suggested that the CD40‐CD154 system may play a crucial role in the aberrant production of immune mediators by SSc fibroblasts, blockage of CD40‐CD154 may be a novel therapeutic strategy for SSc.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40‐CD154 in the phenotype of SSc fibroblasts

et al. 2003

View full text Add to dashboard Cite

show abstract

“…All primary fibroblasts were established by standard explant techniques, as previously described. 34 Strains were cultured in Minimum Essential Medium (MEM; Invitrogen, Carlsbad, CA) supplemented with 10% FBS (Hy Clone Labs, Logan, UT), 2 mmol/L L-glutamine, penicillin (100 units/mL), streptomycin (100 g/mL), and amphotericin (0.25 g/mL) (Invitrogen) at 37°C in 7% CO 2 . In all cases, the resulting cells were morphologically consistent with fibroblasts: they were adherent, did not express CD45, factor VIII, or cytokeratin, but did express vimentin and types I and III collagen.…”

Section: Cells and Reagentsmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

Lehmann

Xia

Kulkarni

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Fibrosis can occur in any human tissue when the normal wound healing response is amplified. Such amplification results in fibroblast proliferation, myofibroblast differentiation, and excessive extracellular matrix deposition. Occurrence of these sequelae in organs such as the eye or lung can result in severe consequences to health. Unfortunately, medical treatment of fibrosis is limited by a lack of safe and effective therapies. These therapies may be developed by identifying agents that inhibit critical steps in fibrotic progression; one such step is myofibroblast differentiation triggered by transforming growth factor-␤1 (TGF␤1). In this study, we demonstrate that TGF␤1-induced myofibroblast differentiation is blocked in human fibroblasts by a candidate endogenous aryl hydrocarbon receptor (AhR) ligand 2-(1=H-indole-3=-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Our data show that ITE disrupts TGF␤1 signaling by inhibiting the nuclear translocation of Smad2/3/4. Although ITE functions as an AhR agonist, and biologically persistent AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause severe toxic effects, ITE exhibits no toxicity. Interestingly, ITE effectively inhibits TGF␤1-driven myofibroblast differentiation in AhR ؊/؊ fibroblasts: Its ability to inhibit TGF␤1 signaling is AhR independent. As supported by the results of this study, the small molecule ITE inhibits myofibroblast differentiation and may be useful clinically as an antiscarring agent.

show abstract

“…CD40 is expressed on a variety of APCs and its ligand, CD40L, is expressed on activated CD4 + and CD8 + T cells; the CD40-CD40L interaction further drives IL-2R expression and antigen-specific T-cell expansion. Several studies described CD40 in non-lymphoid cells too: 86,87 CD40 ligation results in upregulation of surface molecules and cytokine production in cultured cells. Human myoblasts constitutively express CD40: its levels are synergistically increased by TNF-a and IFN-g, 77 while CD40 ligation increases IL-6, IL-8, IL-15 and MCP-1 production and ICAM-1 expression (Figure 4a).…”

Section: Intrinsic Apc Capacities Of Myoblasts and Myocytesmentioning

confidence: 99%

Skeletal muscle cells: from local inflammatory response to active immunity

et al. 2010

View full text Add to dashboard Cite

The skeletal muscles are the major living component of the human body. They are constituted by stable cells, the myofibres, and by adult multipotent stem cells, the satellite cells, which can multiply to regenerate and repair the damaged tissues. Injections of DNA in muscle cells have been used to produce recombinant proteins with opposite goals: somatic reparation of genetic defects, which needs to elicit no inflammatory or immune response, and DNA vaccination, which needs a robust immune response. Because of possible therapeutical interventions, a growing body of information is being produced dealing with every aspect of the myofibres during inflammatory and autoimmune responses: skeletal muscle-antigen presenting cell (APC) interaction and intrinsic APC capabilities of myoblasts and myocytes, the response to released cytokines and their endogenous production, the regulation of Toll-like receptors and major histocompatibility complex expression. According to these data, the muscle tissue is now emerging no longer as a passive bystander, but more as an active player that, when correctly manipulated, can drive tolerance or immunization to these de novo produced proteins. In the present review, we summarize the recent developments on the control of muscle immune function.

show abstract

CD40 Expression by human fibroblasts

Cited by 152 publications

References 41 publications

Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40‐CD154 in the phenotype of SSc fibroblasts

Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40‐CD154 in the phenotype of SSc fibroblasts

The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

Skeletal muscle cells: from local inflammatory response to active immunity

Contact Info

Product

Resources

About