Longitudinal Follow-Up of Chemokine Gene Expression in the Colonic Mucosa of Patients with Tubcrculous Colitis according to Anti-Tuberculosis Treatment

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Abstract

BACKGROUND AND AIMS: Proinflarnmatory cytokines such as IL-l, IL-6 and IL-8 have been implicated in the pathogenesis of ulcerative colitis and Crolm's disease. Tuberculous colitis (TC) could mimic Crohn's disease by its clinical and endoscopical manifestations. In case of pulmonary tuberculosis, TNFa, IL-6 and IL-8 are known to be involved in the pathogenesis. Chemokines belong to proinflanunatory cytokines that play an important role in the recruitment of neutrophils and rnonocytes. However, there has been no attempt to study the chemokines in the colonic mucosa of patients with TC. The goal of thiis study was to explore the chemokine gene expression in the colonic mucosa of patients with TC in comparison with normal controls (NC). In addition, we have followed up the gene expression according to the anti-tuberculosis treatment.
METHODS
Colonoscopic biopsy specimens were obtained from 11 patients with TC, in active or healed state and 10 normal controls. After total tissue RNA was extracted, expression of IL-8 and MCP-1 mRNA was assessed by RT-PCR. The expressed transcripts for chemokines were quantified by quantitative RT-PCR using synthetic standard RNA.
RESULTS
The expression rate of IL-8 and MCP-1 was 45% (5/11) and 55% (6/11) in active TC, 18% (2/11) and 9% (1/11) in healed TC, and 30% (3/10) and 10% (1/10) in normal cantrols, respectively, The frequency of IL-8 and MCP-1 mRNA expression in TC was not significant statistically to NC (p >0.05). The quantitative RT-PCR revealed that the copy number of IL-8 and MCP-1 mRNA were 1.1*10 6 and 9.6*10 5 in active TC, 2.5*10 3 and 1.4*10 3 in healed TC, then 1.6*10 5 and 2.5*10 4 in NC, respectively, Both IL-8 and MCP-1 mRNA were expressed more in the active stage of TC than in the remission stage (p<0.05). The expression of MCP-1 mRNA in patients with TC was significantly higher than those in NC (p<0.05). However, the expression of IL-8 mRNA was not significant (p>0.05).
CONCLUSIONS
Chemokine genes such as IL-8 and MCP-1 are up-regulated in the colonic mucosa of patients with active TC both qualitatively and quantitatively. Expression of these chemokine genes tends to be down-regulated according to the anti-tuberculosis treatment. These findings suggest that chemokines, such as IL-8 and MCP-1, rnay play an important role in the pathogenesis of TC.