Eur Rev Med Pharmacol Sci 2018; 22 (20): 6625-6632
DOI: 10.26355/eurrev_201810_16137

CCL3 participates in the development of rheumatoid arthritis by activating AKT

G. Zhang, H.-B. Liu, L. Zhou, X.-Q. Cui, X.-H. Fan

Department of Orthopedic, Affiliated Hospital of Taishan Medical University, Taian, China. fanxihai666@163.com


OBJECTIVE: To investigate whether CC chemokine 3 (CCL3) could exert a certain effect on rheumatoid arthritis (RA) by regulating inflammatory responses and provide a new direction for the treatment of RA.

PATIENTS AND METHODS: Totally 47 RA patients (10 males and 37 females) with complete clinical data were included. Meanwhile, 27 healthy volunteers with same age and gender were recruited as healthy controls. The mRNA and protein level of CCL3 in the peripheral blood mononuclear cells (PBMCs) of RA patients and normal controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The inflammatory infiltration of synovial tissue was observed by hematoxylin and eosin (HE) staining. Immune fluorescence was used to further analyze the level of CCL3 in T and B cells of synovial tissue in RA patients. Simultaneously, real-time flow cytometry was applied to detect the level of CCL3 in T and B cells of PBMCs in the normal control group and the RA group. Western blot was used to detect the level of pAKT in RA-FLS treated with different concentrations of recombinant human CCL3. Besides, enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) in the culture supernatant of RA-FLS stimulated by different doses of recombinant human CCL3.

RESULTS: The level of CCL3 in peripheral blood and synovial fluid of RA patients was markedly higher than that of normal controls. Inflammatory cells were infiltrated in synovial tissue of RA patients. Meanwhile, CCL3 was mainly expressed in CD4+ T cells. CCL3 treatment in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) could activate the PI3K/AKT signaling pathway to different degrees and increase the expression of cytokines including interleukin-6 (IL-6), IL-1β, TNF-α, and RANKL. These results indicated that CCL3 might participate in the progression of RA by activating AKT.

CONCLUSIONS: We showed that CCL3 enhanced the expression level of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and RANKL by activating the PI3K/AKT signaling pathway. Besides, CCL3 could up-regulate CD4+T cells to mediate the inflammatory response of RA. These findings might provide new directions for the prevention of RA.

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To cite this article

G. Zhang, H.-B. Liu, L. Zhou, X.-Q. Cui, X.-H. Fan
CCL3 participates in the development of rheumatoid arthritis by activating AKT

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 20
Pages: 6625-6632
DOI: 10.26355/eurrev_201810_16137