Yusuke Sakai1, Kazuyuki Uchida, Hiroyuki Nakayama. 1. Department of Veterinary Pathology, Graduated School of Agricultural and Life sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan. anakaya@mail.ecc.u-tokyo.ac.jp
Abstract
OBJECTIVE AND DESIGN: The objective of this paper is to elucidate the factors contributing to the development and regression of trehalose 6,6'-dimycolate (TDM)-induced model of tuberculous granulomatous lesions. MATERIALS AND TREATMENT: BALB/c mice were twice injected i.p. with a 100 μl of w/o/w emulsion (100 μg of TDM, 3.2 μl of Freund's incomplete adjuvant, 3.2 μl of PBS, and 93.6 μl of saline containing 0.2% Tween 20) at a 1 week interval. The mice were killed at days 0, 3, 7, 14, or 21 after the last injection. Three mice were used per group. METHODS: We examined histopathological changes of the lesions and defined the expression levels of cytokines and suppressor of cytokine signaling (SOCS) family proteins by real-time PCR. RESULTS: The levels of inflammatory cytokine, such as TNF-α and IL-1β, paralleled with the size of the lesions and the levels of TGF-β and SOCS-3 were high at regression phase. DISCUSSION: Our results demonstrated that both the down-regulation of inflammatory cytokines and up-regulation of TGF-β and SOCS-3 are crucial for histopathological changes including alteration in the sizes of the lesions and changes in inflammatory cell populations.
OBJECTIVE AND DESIGN: The objective of this paper is to elucidate the factors contributing to the development and regression of trehalose 6,6'-dimycolate (TDM)-induced model of tuberculous granulomatous lesions. MATERIALS AND TREATMENT: BALB/c mice were twice injected i.p. with a 100 μl of w/o/w emulsion (100 μg of TDM, 3.2 μl of Freund's incomplete adjuvant, 3.2 μl of PBS, and 93.6 μl of saline containing 0.2% Tween 20) at a 1 week interval. The mice were killed at days 0, 3, 7, 14, or 21 after the last injection. Three mice were used per group. METHODS: We examined histopathological changes of the lesions and defined the expression levels of cytokines and suppressor of cytokine signaling (SOCS) family proteins by real-time PCR. RESULTS: The levels of inflammatory cytokine, such as TNF-α and IL-1β, paralleled with the size of the lesions and the levels of TGF-β and SOCS-3 were high at regression phase. DISCUSSION: Our results demonstrated that both the down-regulation of inflammatory cytokines and up-regulation of TGF-β and SOCS-3 are crucial for histopathological changes including alteration in the sizes of the lesions and changes in inflammatory cell populations.
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