J Korean Rheum Assoc.  2004 Jun;11(2):77-89.

Interaction between Th1 Cytokine and Th2 Cytokine on the Expression of Chemokine and Adhesion Molecule in Human Mesangial Cells

• Na KS
• Kang TY
• Lee JS
• Park YW
• Lee HS
• Uhm WS
• Kim TH
• Jun JB
• Bae SC
• Lee TY
• Yoo DH

Abstract

PURPOSE: Predominance of IFN-gamma over Th2 cytokines is evident in proliferative lupus nephritis. Th2 cytokines such as IL-10, or IL-4 have been known to suppress Th1 cytokine driven pro-inflammatory responses. However a combination of cytokines can exert variable effects during the evolution of autoimmune diseases depending on the various factors, such as the stage of diseases or local versus systemic expression. To determine whether Th2 cytokines play a pro- or anti-inflammatory role in the local glomerular inflammation induced by IFN-gamma, we studied the effect of IL-10 and IL-4 on the expression of chemokines and adhesion molecules in human mesangial cells stimulated with IFN-gamma. MEHTODS: Human mesangial cells were obtained from 3 patients undergoing nephrectomy. MCP-1, RANTES, ICAM-1, and CD40 expressions were examined in response to various cytokine stimulation; IFN-gamma, IL-10, IL-4, IFN-gamma+IL-10, IFN-gamma+IL-4, and IFN-gamma+IL-10+IL-4, respectively. Expression of MCP-1 mRNA was analyzed by RT-PCR and the levels of MCP-1 and RANTES in the culture supernatants were measured using an enzyme immunoassay. ICAM-1 and CD40 surface expressions were analyzed by flow cytometry.
RESULTS
IFN-gamma increased basal mRNA expression of MCP-1, and IL-10 strongly enhanced the level of MCP-1 mRNA and protein expressions induced by IFN-gamma. IL-4 did not affect significantly on the MCP-1 expression induced by IFN-gamma. Although IFN-gamma increased the concentration of RANTES, IL-10 and IL-4 did not affect IFN-gamma induced RNTES expression. Increased expression of ICAM-1 and CD40 induced by IFN-gamma were not down-regulated by IL-10 or IL-4.
CONCLUSION
Taken together, IL-10 appears to augment local inflammatory reaction though the up-regulation of MCP-1 from mesangial cells in the presence of IFN-gamma rather than inhibit inflammatory response in the pathogenesis of proliferative glomerulonephritis.

Keyword

Cytokines; Chemokines; Adhesion molecules; Mesnagial cell

MeSH Terms

Autoimmune Diseases
Chemokine CCL5
Chemokines
Cytokines
Flow Cytometry
Glomerulonephritis
Humans*
Immunoenzyme Techniques
Inflammation
Intercellular Adhesion Molecule-1
Interleukin-10
Interleukin-4
Lupus Nephritis
Mesangial Cells*
Nephrectomy
RNA, Messenger
Up-Regulation
Chemokine CCL5
Chemokines
Cytokines
Intercellular Adhesion Molecule-1
Interleukin-10
Interleukin-4
RNA, Messenger