The effect of IL-1beta on the expression of inflammatory cytokines and their receptors in human chondrocytes.
Cytokines released at sites of inflammation and infection can alter the normal processes of cartilage turnover, resulting in pathologic destruction or formation. Interleukin (IL)-1beta plays a central role in the pathophysiology of cartilage damage and degradation in arthritis. In the present study, we examined the effect of IL-1beta on the expression of IL-1beta, IL-6, IL-8, IL-11, tumor necrosis factor-alpha (TNF-alpha), and their receptors in human chondrocytes. The cells were cultured either with or without 100 U/ml of IL-1beta for up to 28 days. The level of expression of the cytokines and their receptors was estimated by determining mRNA levels using real-time PCR or by determining protein levels using ELISA. The expression of IL-1beta, IL-8, and TNF-alpha markedly increased in the presence of IL-1beta after day 14 of culture. The expression of IL-6 and IL-11 increased greatly in the presence of IL-1beta on day 1 and after day 14 of culture. The expression of IL-1beta, IL-8, IL-11, and TNF-alpha receptors significantly decreased in the presence of IL-1beta after day 14 of culture, whereas the expression of IL-6 receptor significantly increased. The expression of these cytokines, except for IL-6, decreased with the addition of human IL-1 receptor antagonist. These results suggest that IL-1beta promotes the resolution system of cartilage matrix turnover through an increase in inflammatory cytokine production by chondrocytes and that it also may promote the autocrine action of IL-6 through an increase in IL-6 receptor expression in the cells.
Aida
Yukiko
Y
Department of Crown and Bridge Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Maeno
Masao
M
Suzuki
Naoto
N
Namba
Aki
A
Motohashi
Masafumi
M
Matsumoto
Mitsuhiko
M
Makimura
Masaharu
M
Matsumura
Hideo
H
D019898:Autocrine Communication; D048430:Cell Shape; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D012795:Sialoglycoproteins / Q000494:pharmacology
D016207:Cytokines; C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D018121:Receptors, Cytokine; D012795:Sialoglycoproteins