IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2- dependent prostaglandin synthesis in osteoblasts

• Published in: The Journal of immunology (1950) Vol. 156; no. 2; pp. 758 - 764
• Main Authors: Onoe, Y, Miyaura, C, Kaminakayashiki, T, Nagai, Y, Noguchi, K, Chen, QR, Seo, H, Ohta, H, Nozawa, S, Kudo, I, Suda, T
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.1996
• Subjects: Animals; Bone Resorption - prevention & control; Cells, Cultured; Cyclooxygenase Inhibitors - pharmacology; Depression, Chemical; Dinoprostone - biosynthesis; Enzyme Induction - drug effects; Interleukin-1 - pharmacology; Interleukin-13 - pharmacology; Interleukin-4 - pharmacology; Isoenzymes - antagonists & inhibitors; Mice; Mice, Mutant Strains; Osteoblasts - drug effects; Osteoblasts - metabolism; Prostaglandin-Endoperoxide Synthases - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.156.2.758

Activated T cells secrete the cytokine IL-13, which regulates inflammatory and immune responses. To explore the role of IL-13 in bone metabolism, we examined the effects of the cytokine on bone resorption and PG synthesis in osteoblasts. IL-13 suppressed the bone-resorbing activity stimulated by IL-1 alpha, which was determined by the release of 45Ca from prelabeled mouse long bones. Histologic examinations revealed that IL-1 alpha markedly stimulated bone resorption with increased osteoclast recruitment, and that the simultaneous addition of IL-13 considerably inhibited it. The gamma-chain of IL-2 receptors may be functionally involved in the signal transduction of not only IL-2, but also IL-4, IL-7, and IL-13. Of these cytokines, IL-4 similarly suppressed IL-1 alpha-induced bone resorption, but IL-2 and IL-7 did not. Both IL-13 and IL-4 inhibited PGE2 production stimulated by IL-1 alpha in long bone cultures. Suppression of IL-1 alpha-induced bone resorption by IL-13 and IL-4 was recovered by adding exogenous PGE2 to the long bone cultures. Neither IL-4 nor IL-13 further inhibited IL-1 alpha-induced bone resorption in the presence of indomethacin. To examine the effects of IL-13 on PG synthesis, we measured the mRNA levels of cytosolic phospholipase A2 (cPLA2), constitutively expressed cyclooxygenase (COX-1) and inducible COX (COX-2) in mouse osteoblast-like cells. IL-1 alpha markedly stimulated the mRNA expression of COX-2, but not that of COX-1. Both IL-13 and IL-4 dose-dependently suppressed the IL-1 alpha-induced stimulation of both COX-2 mRNA expression and PGE2 synthesis. A small increase (1.7-fold) in cPLA2 mRNA levels was detected in the cultures with IL-1 alpha, but the expression was not affected by IL-13 or IL-4. These results indicated that IL-13 and IL-4 inhibit bone resorption by suppressing COX-2-dependent PG synthesis in osteoblasts.