Monocyte-Dependent Fibroblast CXCL8 Secretion Occurs in Tuberculosis and Limits Survival of Mycobacteria within Macrophages

摘要: CXCL8 is a chemokine that implicated in the formation of tuberculous (TB) granulomas and immunity to Mycobacterium tuberculosis (Mtb). Fibroblast secretion important for modulating inflammatory responses chronic lung disease arthritis but has not been investigated pathophysiology TB. In this study, we used cellular model examine monocyte/macrophage-dependent stimulation fibroblasts by Mtb regulation secretion, particularly CXCL8. Human grown collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression stable mRNA accompanied >10-fold increase (487 +/- 88 ng/ml vs 48.6 34 controls) at 120 h. Fibroblasts strongly expressed vivo human TB granulomas. Inhibition TNF-alpha or IL-1 CoMTb abrogated induction pretranscriptional level. was NF-kappaB, C/EBP, JNK dependent. Sustained NF-kappaB activation demonstrated beyond 24 h response CoMTb. Exogenous reduced survival within macrophages, inhibition associated intracellular mycobacterial proliferation. These data show have previously unrecognized role inflammation their CXCL8-dependent contribution cell recruitment killing granuloma.