PMID- 37448358
OWN - NLM
STAT- MEDLINE
DCOM- 20240131
LR  - 20240131
IS  - 1872-8081 (Electronic)
IS  - 0951-6433 (Linking)
VI  - 49
IP  - 6
DP  - 2023 Nov-Dec
TI  - P38alpha contributes to TNF-alpha-induced IL-8 production in human gingival cells.
PG  - 1223-1232
LID - 10.1002/biof.1989 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a major inflammatory cytokine that induces 
      interleukin (IL)-8 production. Although some studies have reported the 
      involvement of the p38 MAPK signaling pathway in TNF-alpha-induced IL-8 production, 
      its specific regulatory mechanisms in gingival epithelial cells (GECs) are still 
      poorly understood. In the present study, Ca9-22 cells were used as representative 
      GECs to investigate the effect of p38 signaling on TNF-alpha-induced IL-8 production. 
      We found that TNF-alpha enhanced IL-8 production in Ca9-22 cells by activating the 
      p38 signaling pathway, and one of its isoforms, p38alpha, played a key role. P38alpha 
      deletion markedly inhibited TNF-alpha-induced IL-8 expression in Ca9-22 cells, while 
      p38alpha gene rescue could reverse this effect. Further studies revealed that 
      TNF-alpha-induced IL-8 production was markedly reduced when the threonine 180 and 
      tyrosine 182 p38alpha phosphorylation sites were targeted for mutagenesis to alanine 
      and phenylalanine, respectively, suggesting their critical role in the process. 
      In conclusion, p38alpha plays an important role in TNF-alpha-induced IL-8 production, 
      providing a potential therapeutic target to prevent and treat periodontal 
      disease.
CI  - (c) 2023 International Union of Biochemistry and Molecular Biology.
FAU - Mao, Dan
AU  - Mao D
AUID- ORCID: 0000-0003-1944-7016
AD  - Graduate School of Dentistry, Department of Physiology, Osaka Dental University, 
      Osaka, Japan.
FAU - Inoue, Hiroshi
AU  - Inoue H
AD  - Department of Physiology, Osaka Dental University, Osaka, Japan.
FAU - Notomi, Takuya
AU  - Notomi T
AUID- ORCID: 0009-0004-2507-2809
AD  - Institute of Dental Research, Osaka Dental University, Osaka, Japan.
AD  - Department of Pharmacology, Wakayama Medical University, Wakayama, Japan.
FAU - Goda, Seiji
AU  - Goda S
AD  - Department of Physiology, Osaka Dental University, Osaka, Japan.
LA  - eng
GR  - JP21K10269/the Japan Society for the Promotion of Science KAKENHI/
GR  - 21K09824/the Japan Society for the Promotion of Science KAKENHI/
PT  - Journal Article
DEP - 20230714
PL  - Netherlands
TA  - Biofactors
JT  - BioFactors (Oxford, England)
JID - 8807441
RN  - 0 (Interleukin-8)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Humans
MH  - *Interleukin-8/biosynthesis/genetics
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
MH  - Signal Transduction
MH  - *Tumor Necrosis Factor-alpha/metabolism/pharmacology
MH  - Cell Line
MH  - *Gingiva/metabolism
OTO - NOTNLM
OT  - cytokines
OT  - gene knockout techniques
OT  - immunity
OT  - inflammation
OT  - periodontitis
OT  - signal transduction
EDAT- 2023/07/14 13:06
MHDA- 2023/12/19 06:41
CRDT- 2023/07/14 03:43
PHST- 2023/03/22 00:00 [received]
PHST- 2023/06/21 00:00 [accepted]
PHST- 2023/12/19 06:41 [medline]
PHST- 2023/07/14 13:06 [pubmed]
PHST- 2023/07/14 03:43 [entrez]
AID - 10.1002/biof.1989 [doi]
PST - ppublish
SO  - Biofactors. 2023 Nov-Dec;49(6):1223-1232. doi: 10.1002/biof.1989. Epub 2023 Jul 
      14.