title: Trehalose 6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis induces corneal angiogenesis in rats.
abstract: Neovascularization or angiogenesis is required for the progression of chronic inflammation. The mechanism of inflammatory neovascularization in tuberculosis remains unknown. Trehalose 6, 6'-dimycolate (TDM) purified from Mycobacterium tuberculosis was injected into rat corneas. TDM challenge provoked a local granulomatous response in association with neovascularization. Neovascularization was seen within a few days after the challenge, with the extent of neovascularization being dose dependent, although granulomatous lesions developed 14 days after the challenge. Cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), IL-1beta, and vascular endothelial growth factor (VEGF), were found in lesions at the early stage (within a few days after the challenge) and were detectable until day 21. Neovascularization was inhibited substantially by neutralizing antibodies to VEGF and IL-8 but not IL-1beta. Treatment with anti-TNF-alpha antibodies resulted in partial inhibition. TDM possesses pleiotropic activities, and the cytokine network plays an important role in the process of neovascularization.
authors.affiliation: Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. nsaita@msic.med.osaka-cu.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Saita
authors.forename: N
authors.initials: N
authors.lastname: Fujiwara
authors.forename: I
authors.initials: I
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Soejima
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D003311:Cord Factors / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D009500:Neutralization Tests; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000906:Antibodies; D003311:Cord Factors; D016207:Cytokines