Matrix metalloproteinase‐9 and metalloproteinase‐2 activity and expression is reduced by melatonin during experimental colitis

Abstract

Matrix metalloproteinases (MMPs) are associated with matrix turnover in both physiological and pathological conditions. Several data indicate that MMPs play an important role in the pathogenesis of colitis. Various evidence has documented that the pineal secretory product melatonin exerts an important anti-inflammatory effect in different experimental models including colitis. However, no reports are available on the relationship between the activity and expression of MMPs and anti-inflammatory effect of melatonin. The aim of the present study was to evaluate whether melatonin prevents the experimental colitis in rats by regulating MMP-9 and MMP-2 activity and expression. Colitis was induced by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS). Four days after DNBS administration, colon TNF-alpha production was associated with colon damage. Biochemical methods and zymography were used to analyse MMP-9 and MMP-2 activities in colon tissues from DNBS-injured rats. Our studies reveal that melatonin prevented colon injury and lipid peroxidation in rats at 4 days after DNBS-induced colitis. Melatonin also reduced proMMP-9 and MMP-2 activities that were induced in the colon tissues by DNBS administration. Reduced MMP-9 and MMP-2 activities were associated with reduced expression of TNF-alpha. We conclude that melatonin's ability to reduce DNBS-induced colon injury in rats is related to a reduction in proMMP-9 and MMP-2 activities and expression.

The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

“…Furthermore, it has been shown that MMP-9 is the most abundantly expressed proteinase in IBD. MMP-9 is suggested to be an essential factor for mucosal damage in IBD, as MMP-9 mediates tissue damage during intestinal inflammation [26,27,28,29,30,31,54,55]. …”

“…Of the MMPs, MMP-3 and MMP-9 are consistently upregulated in the animal models of colitis [28,29,30,31]. We and others have reported that MMPs, particularly MMP-9 (type IV collagenase – gelatinase B), is especially important not only in the process of GI tumor progression, but also in the inflammatory and remodeling processes in IBD [32,33,34,35,36].…”

Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation

“…MMPs are involved in the development processes of experimental colitis (Esposito et al 2008b), endometriosis (Paul et al 2008), liver injury (Mishra et al 2011), traumatic experimental spinal cord injury (Esposito et al 2008a), acute ischemic stroke (Ramos-Fernandez et al 2010), and neurodegenerative diseases (Reyes et al 2009, Rosenberg 2009, Bauer et al 2010. Meanwhile, many studies also show that MMPs have contributed to tumor invasion, metastasis, and angiogenesis (Toth & Fridman 2001, Zhang et al 2003, Kessenbrock et al 2010, Pratheeshkumar & Kuttan 2011.…”

Potential Modulation of Disease Activity Indices and Inflammatory Biomarkers in Patients With Active Inflammatory Bowel Disease on Melatonin Adjuvant Therapy

“…Furthermore, it has been reported that reduced MMP-9 and MMP-2 activities are associated with lower expression of TNF-α [3]. Cuzzocrea et al also showed that melatonin monotherapy significantly reduced the appearance of diarrhea and the reduced body weight in rats induced colitis, the effect is mediated by decreasing the production of TNF-α, reducing the activation of NF-κB, decreasing the expression and activity of MMP-9 and -2, and the antiapoptotic effect of melatonin [41].…”