Yadav, P and Bhatt, B and Balaji, KN (2021) Selective activation of MST1/2 kinases by retinoid agonist adapalene abrogates AURKA-regulated septic arthritis. In: Journal of Immunology, 206 (12). pp. 2888-2899.
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Abstract
Septic arthritis is a chronic inflammatory disorder caused by Staphylococcus aureus invasion of host synovium, which often progresses to impairment of joint functions. Although it is known that disease progression is intricately dependent on dysregulated inflammation of the knee joint, identification of molecular events mediating such imbalance during S. aureus-induced septic arthritis still requires detailed investigation. In this article, we report that Aurora kinase A (AURKA) responsive WNT signaling activates S. aureus infection-triggered septic arthritis, which results in inflammation of the synovium. In this context, treatment with adapalene, a synthetic retinoid derivative, in a mouse model for septic arthritis shows significant reduction of proinflammatory mediators with a simultaneous decrease in bacterial burden and prevents cartilage loss. Mechanistically, adapalene treatment inhibits WNT signaling with concomitant activation of HIPPO signaling, generating alternatively activated macrophages. Collectively, we establish adapalene as a promising strategy to suppress S. aureus-induced irreversible joint damage.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Immunology |
| Publisher: | American Association of Immunologists |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | adapalene; aurora A kinase; enzyme; MST1 kinase; MST2 kinase; retinoid; unclassified drug; adapalene; Aurka protein, mouse; aurora A kinase; protein kinase inhibitor; Stk3 protein, mouse; Stk4 protein, mouse, animal experiment; animal model; animal tissue; Article; bacterial arthritis; bacterial load; bone injury; cartilage injury; CFU counting; controlled study; flow cytometry; hippo signaling; histopathology; immunoblotting; immunofluorescence; immunohistochemistry; inflammation; M2 macrophage; micro-computed tomography; mouse; nonhuman; real time reverse transcription polymerase chain reaction; RNA isolation; Staphylococcus aureus infection; transient transfection; Wnt signaling; animal; Bagg albino mouse; disease model; drug effect; immunology; infectious arthritis; microbiology; Staphylococcus aureus; Staphylococcus infection, Adapalene; Animals; Arthritis, Infectious; Aurora Kinase A; Disease Models, Animal; Mice; Mice, Inbred BALB C; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Serine-Threonine Kinase 3; Staphylococcal Infections; Staphylococcus aureus; Wnt Signaling Pathway |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 16 May 2023 09:29 |
| Last Modified: | 16 May 2023 09:29 |
| URI: | https://eprints.iisc.ac.in/id/eprint/81672 |
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