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Induction of necrosis factor- and interleukin-6 in mice in vivo and in murine peritoneal macrophages and human whole blood cells in vitro by Micrococcus luteus teichuronic acids

T. MONODANE, Y. KAWABATA, S. YANG^*, S. HASE and H. TAKADA^*

Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima 890-8544, *Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575 and Department of Chemistry, Graduate School of Science, Osaka University, Toyonka 560-0043, Japan

Corresponding author: Professor H. Takada (email: dent-ht{at}mail.cc.tohoku.ac.jp). Present address: Department of Dental Radiology, Kagoshima University Dental School, Kagoshima 890-8544, Japan.

Received 6 March 2000; revised version accepted 26 May 2000.

Abstract

Earlier studies showed that Micrococcus luteus cells and cell walls induced anaphylactoid reactions leading to death, in some instances within 1 h, in C3H/HeN mice primed with muramyl dipeptide (MDP). They also induced serum cytokines in the surviving mice. The present study investigated the structural components responsible for these activities. Teichuronic acids, a component of M. luteus cell walls, induced tumour necrosis factor- (TNF-) and interleukin-6 (IL-6) in MDP-primed C3H/HeN mice. Peptidoglycans had little effect on the cytokine-inducing activities. Reducing teichuronic acids, i.e., teichuronic acids whose carboxyl groups had been reduced, lost their cytokine-inducing activities. Neither peptidoglycans nor teichuronic acids induced anaphylactoid reactions in the MDP-primed mice. Purified teichuronic acids also induced TNF- and IL-6 production in C3H/HeN murine peritoneal macrophages and human whole-blood cells in the culture, but reduced teichuronic acids did not. The purified teichuronic acids induced no TNF- and only low levels of IL-6 in MDP-primed C3H/HeJ mice, and neither cytokine in peritoneal macrophage cultures from C3H/HeJ mice with a single point of mutation in Toll-like receptor 4 (TLR4) gene. These findings suggest that induction of cytokines by teichuronic acids is mainly TLR4-dependent.

This article has been cited by other articles:

				H. Takada, S. Yokoyama, and Shuhua Yang Mini-review: Enhancement of endotoxin activity by muramyldipeptide Innate Immunity, October 1, 2002; 8(5): 337 - 342. [Abstract] [PDF]

				S. Yang, S. Sugawara, T. Monodane, M. Nishijima, Y. Adachi, S. Akashi, K. Miyake, S. Hase, and H. Takada Micrococcus luteus Teichuronic Acids Activate Human and Murine Monocytic Cells in a CD14- and Toll-Like Receptor 4-Dependent Manner Infect. Immun., April 1, 2001; 69(4): 2025 - 2030. [Abstract] [Full Text] [PDF]