Potential anti-arthritic and anti-inflammatory effects of TNF- α processing inhibitor-1 (TAPI-1): A new approach to the treatment of S. aureus arthritis.

This study aimed to unveil the potential anti-arthritic effects of TAPI-1 (TNF-α processing inhibitor-1), an inhibitor that inhibits TACE (TNF-α converting enzyme) mediated release of soluble TNF-α and its receptors along with attenuation of other inflammatory and joint destructive factors responsible for the progression of arthritis. Male Swiss albino mice were inoculated with live S. aureus (5 × 106 cells/mouse) for the development of septic arthritis. TAPI-1 was administered intraperitoneally (10 mg/kg body weight) post S. aureus infection at regular intervals. Throughout the experiment, the severity of arthritis was obtained to be significantly low after TAPI-1 administration. Arthritis index and histopathology confirmed effectiveness of TAPI-1 in mitigating inflammation induced paw swelling and less bone-cartilage destruction in the arthritic knee joints. Lower levels of soluble tumor necrosis factor alpha (sTNF-α) and soluble tumor necrosis factor alpha receptor-1 (sTNFR-1) were detected in the TAPI-1 treated group suggesting TAPI-1 mediated blocking of TACE with subsequent inhibition of TNF-α signalling. Treatment with TAPI-1 lowered the levels of reactive species; matrix metalloproteinase-2 (MMP-2), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteopontin (OPN) denoting less matrix degradation and less osteoclastic bone resorption. Together, this experimental work authenticates TAPI-1 as an alternative therapeutic intervention for the tr...
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research