Overexpression of beta-arrestin 2 in peripheral blood mononuclear cells of patients with cryptococcal meningitis.
Cryptococcal meningitis is often associated with elevated IL-10 levels, which suggest a dysregulation in the antifungal immune response. beta-Arrestin 2 plays a major role in desensitization of G-protein-coupled receptors involved in the immune responses, provides a scaffolding platform for modification of many signal transduction proteins, and binds Src and MAP kinases family members. This study compared the levels of beta-arrestin 2 mRNA and protein in peripheral blood mononuclear cells (PBMC) of patients with cryptococcal meningitis detected. The interferon-gamma (IFN-gamma) serum concentration was determined with enzyme-linked immunosorbent assay (ELISA) to reveal its relationship with beta-arrestin 2. The effect of modulation of beta-arrestin 2 on cytotoxic activity against Cryptococcus was explored via transfection and interference of beta-arrestin 2. PBMCs of patients with cryptococcal meningitis exhibited significantly elevated levels of beta-arrestin 2 and a positive correlation between beta-arrestin 2 and IL-10 levels existed in patients' serum, but a negative correlation was found between beta-arrestin 2 and IFN-gamma expression. In conclusion, elevated expression of beta-arrestin 2 in PBMCs of patients with cryptococcal meningitis correlated with a reduced cytotoxic activity against Cryptococcus. This study suggests that reduced beta-arrestin 2 mRNA levels or inhibition of beta-arrestin 2 activity may augment INF-gamma production, and ultimately, the anti-Cryptococcus immune response of infected patients.
Xia
Rong
R
Department of Transfusion, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Hu
Zhide
Z
Sun
Yi
Y
Chen
Sunxiao
S
Gu
Mingli
M
Zhou
Ye
Y
Han
Zhijun
Z
Zhong
Renqian
R
Deng
Anmei
A
Wen
Hai
H
D019390:Arrestins / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D019390:Arrestins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D016753:Interleukin-10; D007371:Interferon-gamma