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.

Abstract

Treatment of septic arthritis has become more challenging due to the rise of multidrug resistant strains of Staphylococcus aureus (S. aureus) in recent years. Failure of antibiotic therapies has compelled to initiate the search for new alternatives. 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 treatment of S. aureus arthritis.

• Authors: Sahin Sultana, Biswadev Bishayi
• Journal: Immunobiology (Immunobiology) Vol. 225 Issue 2 Pg. 151887 (03 2020) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 31822434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Anti-Inflammatory Agents
• Dipeptides
• Hydroxamic Acids
• N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Arthritis, Experimental (drug therapy, metabolism, microbiology)
• Arthritis, Infectious (drug therapy, metabolism)
• Bone and Bones (drug effects, metabolism, microbiology)
• Dipeptides (physiology)
• Disease Models, Animal
• Hydroxamic Acids
• Inflammation (drug therapy, metabolism)
• Joints (drug effects, metabolism, microbiology)
• Male
• Mice
• Signal Transduction (drug effects)
• Staphylococcal Infections (drug therapy, metabolism)
• Staphylococcus aureus (drug effects, pathogenicity)
• Tumor Necrosis Factor-alpha (metabolism)