PMID- 36263937
OWN - NLM
STAT- MEDLINE
DCOM- 20230530
LR  - 20230530
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 45
IP  - 3
DP  - 2023 Jun
TI  - Impact of interleukin-32alpha on T helper cell-related cytokines, transcription 
      factors, and proliferation in patients with type 2 diabetes mellitus.
PG  - 268-276
LID - 10.1080/08923973.2022.2138430 [doi]
AB  - OBJECTIVE: The ability of interleukin (IL)-32alpha to induce T helper (Th) 1, Th17, 
      and Treg cytokines (interferon gamma [IFN-gamma], IL-17, and IL-10, respectively), 
      and transcription factors ([signal transducer and activator of transcription 
      (STAT) 1 and T-box (T-bet) for Th1, STAT3 and retinoid-related orphan receptor 
      (ROR)-gammat for Th17, and STAT5 and forkhead box P3 (Foxp3) for Treg]) were 
      investigated in type 2 diabetes mellitus (T2DM). IL-32alpha effects on Th cell 
      proliferation and related factors including IL-2 and NF-kappaB were also explored. 
      METHODS: Serum levels of IL-32alpha in 31 patients and 31 healthy controls (HCs) were 
      determined by ELISA assay. CD4(+) T cells cultured with polyclonal activators in 
      the presence and absence of recombinant IL-32alpha (rIL-32alpha). Gene expressions in 
      cultured Th cells were assessed with real-time PCR. Cytokines in supernatants 
      were measured with ELISA. Proliferation experiments were assessed by flow 
      cytometry. RESULTS: The patients showed significant increase in IL-32alpha levels 
      compared with HCs and its levels were positively correlated with fasting plasma 
      glucose (FPG) and hemoglobin A1c (HbA1c). rIL-32alpha enhanced IL-17 and IL-2 
      production, increased ROR-gammat and NF-kappaB expression, and enhanced Th proliferation 
      in both patients and HCs. In patients, IL-17, ROR-gammat, NF-kappaB, and proliferation 
      levels were higher than those in HCs, in cultures with and without rIL-32alpha 
      (rIL-32alpha(+) and rIL-32alpha(-)). IL-2 levels in rIL-32alpha(+)cultures of patients were 
      significantly higher than the HCs, and it was positively correlated with 
      proliferation rate and NF-kappaB expression. CONCLUSIONS: Aberrant IL-32alpha levels are 
      participated in T2DM pathogenesis. IL-32alpha potently induces Th17-related factors 
      and amplifies the proliferative function of T cells.HighlightsEnhanced serum 
      levels of IL-32alpha in T2DM patients was correlated with FPG and HbA1c.IL-32alpha 
      increases ROR-gammat expression and IL-17 production, and induces Th17 cells.IL-32alpha 
      enhances NF-kappaB expression and IL-2 production, and promotes Th 
      proliferation.IL-32alpha is more effective for inducing Th17 cells and proliferation 
      in the patients.IL-32alpha axis could be mentioned as a future therapeutic goal for 
      the T2DM.
FAU - Borzouei, Shiva
AU  - Borzouei S
AUID- ORCID: 0000-0001-6826-9872
AD  - Department of Internal Medicine, School of Medicine, Hamadan University of 
      Medical Sciences, Hamadan, Iran.
FAU - Gholamian-Hamadan, Mohammad
AU  - Gholamian-Hamadan M
AUID- ORCID: 0000-0003-3433-6496
AD  - Department of Immunology, School of Medicine, Hamadan University of Medical 
      Sciences, Hamadan, Iran.
FAU - Behzad, Mahdi
AU  - Behzad M
AUID- ORCID: 0000-0002-8940-3847
AD  - Department of Immunology, School of Medicine, Hamadan University of Medical 
      Sciences, Hamadan, Iran.
LA  - eng
PT  - Journal Article
DEP - 20221027
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (Cytokines)
RN  - 0 (Transcription Factors)
RN  - 0 (Interleukin-17)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (Glycated Hemoglobin)
RN  - 0 (Interleukin-2)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Humans
MH  - *Cytokines/metabolism
MH  - Transcription Factors/metabolism
MH  - Interleukin-17/metabolism
MH  - NF-kappa B/metabolism
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
MH  - *Diabetes Mellitus, Type 2
MH  - Glycated Hemoglobin
MH  - Interleukin-2/metabolism
MH  - T-Lymphocytes, Regulatory/metabolism
MH  - Th17 Cells/metabolism
MH  - Cell Proliferation
MH  - Forkhead Transcription Factors/metabolism
OTO - NOTNLM
OT  - IL-32
OT  - STAT
OT  - T cell
OT  - proliferation
OT  - transcription factor
OT  - type 2 diabetes mellitus
EDAT- 2022/10/21 06:00
MHDA- 2023/05/30 06:42
CRDT- 2022/10/20 06:53
PHST- 2023/05/30 06:42 [medline]
PHST- 2022/10/21 06:00 [pubmed]
PHST- 2022/10/20 06:53 [entrez]
AID - 10.1080/08923973.2022.2138430 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2023 Jun;45(3):268-276. doi: 
      10.1080/08923973.2022.2138430. Epub 2022 Oct 27.