Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage differentiation through the activation of caspase-1 in vitro
- Equal contributors
1 Biochip Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea
2 Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
3 Department of Otolaryngology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea
4 High-Enthalpy Plasma Research Center, Chonbuk National University, 664-14, 1Ga Deokjin-dong, Deokjin-gu, Jeonju, 561-756, Republic of Korea
Arthritis Research & Therapy 2012, 14:R259 doi:10.1186/ar4104Published: 28 November 2012
Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated.
We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells.
Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation.
Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.