The importance of calcium-binding proteins in angiogenesis and in

The importance of calcium-binding proteins in angiogenesis and inflammation has also been reported earlier, proving that calcium-binding proteins are also potent angiogenic mediators [7, 35]. Earlier, our laboratory reported the proinflammatory role of CaMBPs isolated from ascites fluid from mouse mammary carcinoma cell lines that could activate respiratory burst [20]. Consistent

with previous reports, NAP isolated from SF of RA induces oedema in the footpad, revealing proinflammatory activity. Reports showing that the presence of CaMBPs at sites of acute and chronic inflammation have long been noted. Indeed, assessment of serum levels of CaMBP molecules have been suggested to track disease activity in patients with inflammatory disorders such as ulcerative colitis, chronic inflammatory bowel disease, psoriatic arthritis (sPA) ABT-888 clinical trial Peptide 17 chemical structure and RA [35], and is also a valuable marker [36-38]. We have developed a model using NAP similar to the AIA model of RA in Wistar rats to examine the role of NAP in the development

of this disease. Our results show that the levels of NAP and VEGF in AIA and NIA animals were found to increase in serum. Similar to other reports [36, 39, 40], NAP levels in the serum elevated gradually after the onset of arthritis, with the highest level at 21 days after induction. Treatment with antibodies such as anti-TNF-α antibody has influenced the expression of other proinflammatory cytokines involved in RA [41]. Antibodies against calcium- and

membrane-binding protein have reduced the accumulation of neutrophils in air pouch models of acute gouty arthritis [42]. Annexins are another class of CaMBPs which induce angiogenesis via stimulation of VEGF production. S100A4 induce angiogenesis through interaction with annexin II on the surface of endothelial cells [36]. Treatment with anti-S100A12 antibodies, anti-renal cell carcinoma antigen (RAGE) antibodies and soluble-RAGE (sRAGE) and CaMBPs have reduced inflammation effectively in animal models of arthritis [7]. Consistent with Fossariinae previous reports, our data demonstrate that treatment with anti-NAP mAb of AIA or NIA rat models effectively reduces paw swelling, degree of redness and flexibility of the rear ankle joints, indicating the neutralization and potential therapeutic effect of these antibodies. Quantification of growth factor VEGF and NAP by ELISA indicated an increased amount of VEGF or NAP correlating with the progression of the disease, whereas in the case of anti-NAP mAb-treated animals, a decrease in the amount of NAP or VEGF levels in sera was evident. The effect of anti-NAP mAb on proliferation of endothelial cells is especially visible when observing blood vessel formation in synovium. Histopathological studies showed clearly the inhibition of blood vessel formation in H&E staining.

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