Histopathological features and expression profiles of cytokines, chemokines and SOCS family proteins in trehalose 6,6'-dimycolate-induced granulomatous lesions.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
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
Yusuke
Y
Sakai
Kazuyuki
K
Uchida
Hiroyuki
H
Nakayama
D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003311:Cord Factors / Q000009:adverse effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006099:Granuloma / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D018925:Chemokines; D003311:Cord Factors; D016207:Cytokines; D050826:Suppressor of Cytokine Signaling Proteins