PMID- 35430508
OWN - NLM
STAT- MEDLINE
DCOM- 20220504
LR  - 20220531
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 233
DP  - 2022 May
TI  - P38alpha deficiency in macrophages ameliorates murine experimental colitis by 
      regulating inflammation and immune process.
PG  - 153881
LID - S0344-0338(22)00124-8 [pii]
LID - 10.1016/j.prp.2022.153881 [doi]
AB  - INTRODUCTION: P38alpha is a mitogen-activated protein kinase (MAPK) that mediates 
      inflammatory responses. P38alpha alterations have been associated with the 
      inflammation-related diseases. However, the role of macrophages-derived p38alpha in 
      dextran sulfate sodium (DSS)-induced murine experimental colitis remains unclear. 
      OBJECTIVES: We characterized the role of macrophages-derived p38alpha in DSS-induced 
      colitis. METHODS: The expression of macrophage-derived p38alpha in human colitis and 
      normal tissues was measured by immunohistochemistry (IHC) and fluorescence in 
      situ hybridization (FISH) analysis. Macrophage-specific p38alpha knockout (p38alpha(DeltaMphi)) 
      and wild type (WT) mice administrated by 3% DSS were used to establish 
      experimental colitis. The alterations in inflammatory cytokines, intestinal 
      epithelial barrier, cell proliferation and cell apoptosis between p38alpha(DeltaMphi) and 
      WT groups were determined by IHC, immunofluorescence (IF), TdT-mediated dUTP 
      Nick-End Labeling (TUNEL) and Western blot analyses. The enriched pathways 
      between p38alpha(DeltaMphi) and WT groups were identified by RNA-seq and KEGG analysis. 
      SB203580 and BIRB796 as the p38 MAPK inhibitors were used to treat DSS-induced 
      colitis. RESULTS: p38alpha was co-localized with CD68 in the cytoplasm and their 
      co-expression indicated an increased level in colitis tissues as compared with 
      the normal tissues. P38alpha deficiency in macrophages was sufficient to suppress the 
      exacerbated clinical symptoms and inflammation responses in experimental colitis, 
      followed by reducing cytokine release, increasing MUC-2 and Claudin-2 secretion 
      and promoting colonic mucosa repair. Further investigations validated that the 
      immune process-related factors such as Lgals9, Rtp4, Ddx60, Nlrp1b, Hsh2d, Oas2 
      and Oas3 were upregulated in colon tissues from p38alpha(DeltaMphi) group as compared with 
      the WT group. Inhibition of p38 MAPK attenuated DSS-induced colitis. CONCLUSION: 
      Our findings demonstrated that p38alpha deficiency in macrophages ameliorated murine 
      experimental colitis by regulating inflammation and immune process.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China.
FAU - Liang, Rui
AU  - Liang R
AD  - Department of Geriatrics and National Clinical Research Center for Geriatrics, 
      West China Hospital, Sichuan University, Chengdu, China.
FAU - Yi, Youcai
AU  - Yi Y
AD  - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China.
FAU - Zhu, Jinshui
AU  - Zhu J
AD  - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China. Electronic address: zhujs1803@163.com.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China. Electronic address: jing5522724@vip.163.com.
LA  - eng
PT  - Journal Article
DEP - 20220409
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Cytokines)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - *Colitis/chemically induced
MH  - Cytokines
MH  - Humans
MH  - Immunity
MH  - In Situ Hybridization, Fluorescence
MH  - Inflammation
MH  - Macrophages
MH  - Mice
MH  - *Mitogen-Activated Protein Kinase 14
MH  - p38 Mitogen-Activated Protein Kinases
OTO - NOTNLM
OT  - Colitis
OT  - Immune process
OT  - Inflammation response
OT  - Macrophages
OT  - p38 MAPK
EDAT- 2022/04/18 06:00
MHDA- 2022/05/06 06:00
CRDT- 2022/04/17 20:21
PHST- 2021/11/24 00:00 [received]
PHST- 2022/03/23 00:00 [revised]
PHST- 2022/04/01 00:00 [accepted]
PHST- 2022/04/18 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2022/04/17 20:21 [entrez]
AID - S0344-0338(22)00124-8 [pii]
AID - 10.1016/j.prp.2022.153881 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2022 May;233:153881. doi: 10.1016/j.prp.2022.153881. Epub 2022 
      Apr 9.