Suppressive effects of ketotifen on Th1- and Th2-related chemokines of monocytes.

Abstract

Ketotifen is a mast cell stabilizer and useful in younger children with allergic diseases such as asthma and allergic rhinitis. Macrophage-derived chemokine (MDC) is a T-helper cell type 2 (Th2)-related chemokine involved in recruitment of Th2 cells toward allergen-challenged inflammation. However, the Th1-related chemokines, interferon-inducible protein 10 (IP-10)/CXCL10, and the monokine induced by interferon-gamma (MIG)/CXCL9 are also important in allergen-induced asthma in animal models. We investigated the effects of ketotifen on the expression of Th1- and Th2-related chemokines of human monocytes in vitro and ex vivo. Ketotifen (5-50 microM) significantly down-regulated lipopolysaccharide (LPS)-induced MDC, MIG and IP-10 (p < 0.05, each comparison) in THP-1 cells and human primary monocytes in a dose-dependent manner. SB203580 [p38-mitogen-activated protein kinase (MAPK) inhibitor] suppressed LPS-induced MDC and IP-10 expression, and PD98059 (ERK-MAPK inhibitor) could only suppress LPS-induced IP-10, but not MDC expression. LPS-induced pp38 and p-ERK expression of THP-1 monocytic cells was suppressed by ketotifen. These data demonstrate that ketotifen is effective in down-regulating LPS-induced MDC, MIG and IP-10, which play important roles in the pathogenesis of airway inflammation. The suppressive effect on MDC and IP-10 may, at least in part, involve the down-regulation of LPS-induced p38 and ERK-MAPK expression.

• Authors: Chih-Hsing Hung, Jau-Ling Suen, Yi-Ming Hua, Wen Chiang, Hui-Chiu Chang, Chun-Nan Chen, Yuh-Jyh Jong
• Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology (Pediatr Allergy Immunol) Vol. 18 Issue 5 Pg. 378-84 (Aug 2007) ISSN: 0905-6157 [Print] England
• PMID: 17617806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Allergic Agents
• Chemokines
• Immunosuppressive Agents
• Ketotifen

Topics

• Anti-Allergic Agents (pharmacology)
• Cell Line, Tumor
• Chemokines (antagonists & inhibitors, biosynthesis)
• Humans
• Immunosuppressive Agents (pharmacology)
• Ketotifen (pharmacology)
• Monocytes (drug effects, immunology)
• Th1 Cells (drug effects, immunology, metabolism)
• Th2 Cells (drug effects, immunology, metabolism)