Naslov
The role of Mid1-PP2A axis in inflammation-induced joint damage in antigen-induced arthritis

Autori
Lukač, Nina ; Flegar, Darja ; Kelava, Tomislav ; Šućur, Alan ; Zrinski Petrović, Katerina ; Šisl, Dino ; Filipović, Maša ; Katavić, Vedran ; Grčević, Danka ; Kovačić, Nataša.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Annual meeting of the Croatian Immunological Society 2019 / - , 2019, 52-52

Skup
Annual meeting of the Croatian Immunological Society 2019

Mjesto i datum
Rovinj, Hrvatska, 11.10.2019. - 12.10.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
arthritis, myeloid cells, Midline 1

Sažetak
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune joint disease which often causes structural joint damage not reversible by currently available therapeutics, urging discovery of new molecular mediators for therapeutic targeting. In a murine model of RA, antigen- induced arthritis(AIA) we have previously shown that destructive AIA is characterized by accumulation of synovial myeloid cells which up- regulate Mid1 gene. Due to the previously described involvement of Mid1 in pathogeneses of immune-mediated diseases, the objective of this study was to evaluate the role of Mid1 in AIA. MATERIALS AND METHODS: AIA was induced in C57BL6 mice by immunization with methylated bovine serum albumin (mBSA) and subsequent intra-articular injection of mBSA. Expression of Mid1 and pro- inflammatory cytokines was assessed by qRT-PCR. Mice were treated with metformin, which prevents Mid1-mediated ubiquitinilation of PP2A, and thus has an anti-inflamatory effect, at a daily dose of 1g/kg, to evaluate the effects of blocking the Mid1-mediated inflammation on arthritis development and subchondral bone resorption (assesed by μ-CT). RESULTS: Mid1 was up-regulated in knee joints early after arthritis induction. Its expression positively correlated with severity of arthritis assesed by knee diameter measurement and levels of pro-inflammatory cytokines, IL-1, IL-6 and TNF. Although Mid1 is positioned on the X-chromosome, its expression was up regulated in arthritic joints of both male and female mice. Metformin treatment ameliorated the severity of arthritis and arthritis-induced subchondral bone resorption. CONCLUSION: Inhibition of Mid1- mediated PP2A degradation by metformin might aid to therapeutic management of inflammatory arthritides.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA