Cytokine Profile of Human Abdominal Aortic Aneurysm: Involvement of JAK/STAT Pathway

人类腹主动脉瘤的细胞因子概况:JAK/STAT 通路的参与

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作者:Tomokazu Ohno, Hiroki Aoki, Satoko Ohno, Michihide Nishihara, Aya Furusho, Shinichi Hiromatsu, Hidetoshi Akashi, Yoshihiro Fukumoto, Hiroyuki Tanaka

Conclusion

The findings of the present study suggested that AAA tissue exhibits a stereotypical profile of cytokine secretion, where JAK/STAT pathway may play a role in regulating a subset of cytokines. Identification of such a cytokine profile may reveal potential diagnostic markers and therapeutic targets for AAA.

Methods

We analyzed the comprehensive cytokine secretion profiles of 52 cytokines from human AAA in four patients with AAA using fluorescent beads-based multiplex assay. Further, the effect of janus kinase (JAK) inhibition by pyridone 6 on cytokine profiles was also evaluated.

Objective

Abdominal aortic aneurysm (AAA) is characterized by inflammation and destruction of normal tissue architecture. The present study aimed to evaluate the inflammatory signaling cascade by analyzing the cytokines of AAA tissue. Materials and

Results

Cytokine secretion profiles were found to be similar among the four patients. A high level of JAK/signal transducers and activator of transcription (STAT) pathway activity in AAA tissue in culture was maintained, which may be attributed to the secretion of endogenous JAK-activating cytokines. Inhibition of JAK by pyridone 6 resulted in the suppression of STAT3 phosphorylation and secretion of a subset of chemokines and JAK-activating cytokines. However, the inhibition of JAK had no effect on the secretion of matrix metalloproteinase (MMP)-2, MMP-9, or TGF-β family that is responsible for the metabolism of extracellular matrix.

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