The Effect of Anti-Inflammatory Drugs on MEFV, PSTPIP1, Siva, and ASC Gene Expression Levels

Abstract

Aim: Familial Mediterranean Fever (FMF) is the one of the most common autoinflammatory diseases. FMF is characterized by fever attacks and inflammation and colchicine treatment reduces the frequency and severity of FMF attacks. The FMF gene, MEditerranean FeVer (MEFV), encodes a protein called Pyrin, which regulates inflammation through its interactions with several proteins. These proteins are; Apoptosis-associated speck like protein with a CARD (ASC), Proline serine threonine phosphatase interacting protein 1 (PSTPIP1), 14.3.3 proteins and Siva proteins. In this study, we aimed to study the effect of anti-inflammatory drugs with different mechanisms of action on MEFV, PSTPIP1, Siva, and ASC gene expression levels. Material and Methods: We used differentiated monocytic cell line called THP-1 cells. Cells treated with colchicine, naproxen, prednol-L, acetylsalicylic acid, or azathioprine w and w/o lipopolysaccharide (LPS). After incubation, quantitative RT-PCR (qRT-PCR) was performed to measure MEFV, PSTPIP1, Siva, and ASC gene expression levels. Results: MEFV gene expression level was down regulated in colchicine, naproxen, and azathioprine treated cells whereas PSTPIP1 gene expression level was down regulated in naproxen and azathioprine treated cells with LPS. Siva gene expression level was up regulated in all treatments although ASC gene expression level was up regulated in only prednol-L treated cells with LPS. Conclusion: These anti-inflammatory drugs are known to have different mechanisms of action however they are all used to treat pain or inflammation. Since Pyrin, PSTPIP1, Siva, and ASC have pro and anti-inflammatory roles, the results showing an alteration in gene expression levels with specific drugs may indicate the possible mechanisms of therapeutic action.