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

Öz

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.

Anahtar Kelimeler

• Familial Mediterranean Fever (FMF)
• Anti-inflammatory drugs
• Inflammation
• Inflammation-related genes

Anti-inflamatuvar ilaçların MEFV, PSTPIP1, Siva ve ASC gen ifade düzeylerine olan etkisi

Öz

Amaç: Ailevi Akdeniz Ateşi (AAA) en sık görülen ve tekrarlayan ateş atakları ve ağrılı inflamasyon ile karakterize olan otoinflamatuvar bir hastalıktır. Kolşisin tedavisi, AAA ataklarının sıklığını ve şiddetini azaltır. Pyrin adlı bir proteini kodlayan AAA geni, MEditerranean FeVer (MEFV) geni tarafından kodlanmakta ve ilişkili olduğu proteinler aracılığıyla inflamasyonu düzenlemektedir. İlişkili olduğu bu proteinler; Apoptozla ilişkili benek benzeri protein CARD(ASC), Prolin serin treonin fosfataz etkileşimli protein 1(PSTPIP1), 14.3.3 proteini ve Siva proteinleridir. Bu çalışmada, farklı etki mekanizmalarına sahip anti-inflamatuvar ilaçların MEFV, PSTPIP1, Siva ve ASC gen ifade seviyeleri üzerindeki etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Hücre hattı olarak farklılaşmış monositik hücreleri olan THP-1 hücreleri kullanılmıştır. Kolşisin, naproksen, prednol-L, asetilsalisilik asit veya azatiyoprin ilaçları, lipopolisakkarit (LPS) varlığında ve yokluğunda hücrelere uygulanmıştır. MEFV, PSTPIP1, Siva ve ASC gen ifade seviyelerini ölçmek için kantitatif RT-PCR(qRT-PCR) yapılmıştır. Bulgular: LPS varlığında, MEFV geni ifade seviyesi, kolşisin, naproksen ve azatioprin uygulanan hücrelerde azalırken, PSTPIP1 gen ifade seviyesi, naproksen ve azatioprin uygulanan hücrelerde azalmıştır. LPS varlığında, Siva gen ifade seviyesi tüm ilaç uygulamalarında artarken, ASC gen ifadesi sadece LPS ve prednol-L uygulamalarında artmıştır. Sonuç: Tüm bu anti-inflamatuvar ilaçların farklı etki mekanizmaları olduğu bilinmektedir, ancak hepsi ağrı veya iltihabı tedavi etmek için kullanılmaktadır. Pyrin, PSTPIP1, Siva ve ASC proteinleri pro ve anti-inflamatuvar rollere sahip olduğundan, genlerin ifade düzeylerindeki değişiklik ilaçların terapötik etkilerinin olası mekanizmalarını aydınlatmada yol gösterici olabilecektir.

Anahtar Kelimeler

• Ailevi Akdeniz Ateşi (AAA)
• Anti-inflamatuvar ilaçlar
• İnflamasyon
• İnflamasyonla ilişkili genler

Kaynakça

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