Related Experiment Videos
Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and
M J Yellin1, S Winikoff, S M Fortune
1Department of Medicine, Columbia University, New York, New York 10032, USA.
Insights
Fibroblasts express CD40, a molecule crucial for immune responses. Cytokines like interferon-gamma regulate fibroblast CD40, influencing cell activation and proliferation, highlighting a novel role for fibroblasts in immune signaling.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- CD40 is a key B cell surface molecule involved in immune regulation.
- CD40 expression extends beyond immune cells to include monocytes, dendritic cells, epithelial cells, and basophils.
- The expression and function of CD40 on fibroblasts were previously uncharacterized.
Purpose of the Study:
- To investigate CD40 expression on synovial membrane (SM) and dermal fibroblasts.
- To determine the functional significance of fibroblast CD40.
- To explore the regulation of fibroblast CD40 expression by cytokines.
Main Methods:
- In vitro culture of synovial membrane and dermal fibroblasts.
- Flow cytometry to assess CD40 expression.
- Stimulation with recombinant interferon-gamma (rINF-gamma), interleukin-1 alpha, and tumor necrosis factor-alpha.
- Analysis of CD54, CD106, and IL-6 production.
- Assessment of fibroblast proliferation.
Main Results:
- Fibroblasts express cell surface CD40 in vitro.
- Fibroblast CD40 expression decreases with time in culture but is upregulated by rINF-gamma.
- rINF-gamma-induced CD40 upregulation is enhanced by interleukin-1 alpha and tumor necrosis factor-alpha.
- CD40 ligation upregulates CD54 and CD106 on SM fibroblasts.
- CD40 ligation augments IL-6 production and induces proliferation in SM fibroblasts.
- rINF-gamma enhances CD40L-CD40-induced fibroblast proliferation.
Conclusions:
- Fibroblasts express functional CD40 on their surface.
- Cytokines significantly regulate fibroblast CD40 expression and activity.
- CD40 ligation promotes fibroblast activation, adhesion molecule expression, and proliferation, suggesting a role in inflammatory and fibrotic conditions.
Abstract:
CD40 was originally described as a functionally significant B cell surface molecule. However, CD40 is also expressed on monocytes, dendritic cells, epithelial cells, and basophils. We now report that synovial membrane (SM) or dermal fibroblasts also express cell surface CD40 in vitro. Fibroblast CD40 expression declines with increasing time in culture and recombinant interferon-gamma (rINF-gamma) induces fibroblast CD40 up-regulation. This effect of rINF-gamma is augmented by recombinant interleukin-1 alpha or recombinant tumor necrosis factor-alpha. CD40 expression on fibroblasts is functionally significant because CD40L-CD40 interactions induce SM fibroblast CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1) up-regulation. Moreover, ligation of CD40 augments IL-6 production by SM fibroblasts and induces fibroblasts to proliferate. In addition, rINF-gamma enhances the effect of CD40L-CD40 interactions on fibroblast proliferation. Taken together, these studies show that fibroblasts can express CD40, cytokines can regulate fibroblast CD40 expression, and CD40 ligation induces fibroblast activation and proliferation.