PMID- 28951356
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200226
IS  - 1673-4254 (Print)
IS  - 2663-0842 (Electronic)
IS  - 1673-4254 (Linking)
VI  - 37
IP  - 9
DP  - 2017 Sep 20
TI  - [Expressions of inflammatory cytokines in mouse peritoneal macrophages induced by 
      MRP8/MRP14 in vitro].
PG  - 1164-1170
AB  - OBJECTIVE: To investigate MRP8/MRP14-induced expression of inflammatory cytokines 
      in mouse peritoneal macrophages and explore the mechanism. METHODS: Tumor 
      necrosis factor-alpha (TNF-alpha), interferon-gamma inducible protein 10 (IP-10), 
      interleukin-2 (IL-2), IL-6, IL-5 and interferon-gamma (IFN-gamma) proteins in the culture 
      supernatants of mouse peritoneal macrophages treated with recombinant MRP8/MRP14 
      were quantified using Luminex xMAP system. TNF-alpha, IP-10 and IL-6 levels were 
      detected in the culture supernatants of the peritoneal macrophages after 
      treatment with different domains of MRP14. Western blotting was used to detect 
      the phosphorylation of p38 MAPK, JNK and ERK in the cells after MRP8/MRP14 
      treatment. The effects of p38 MAPK, JNK, ERK inhibitors, TLR4 or RAGE receptor 
      antagonists on MRP8/MRP14-induced expressions of TNF-alpha, IP-10 and IL-6 were 
      tested. RESULTS: MRP8/MRP14 significantly increased TNF-alpha, IP-10 and IL-6 levels 
      in mouse peritoneal macrophages by 98.2, 378.6 and 6.3 folds (P<0.01), 
      respectively, but did not obviously affect IL-2, IL-5 and IFN-alpha levels. MRP14 
      protein and its calcium binding motifs such as EF hand-1, EF hand-2, EF hand-1+2, 
      but not CT terminal domain, all induced TNF-alpha, IP-10 and IL-6 expressions 
      (P<0.01). Phosphorylation of p38 MAPK, JNK and ERK were detected by Western 
      blotting in the cells at 1 h after MRP8/MRP14 stimulation and sustained to 2 h. 
      Compared with MRP8/MRP14, SB203580 (p38 MAPK inhibitor) significantly inhibited 
      TNF-alpha, IP-10 and IL-6 expression (P<0.05), and SP600125 (JNK inhibitor) inhibited 
      the expression of TNF-alpha and IP-10 (P<0.05) but not IL-6, PD98059 and U0126 (ERK 
      and MEK1/2 inhibitor) reduced IL-6 expression (P<0.05). TNF-alpha, IP-10 and IL-6 
      levels were inhibited by TAK242 (P<0.05); IL-6 level in the cells was also 
      partially inhibited by RAGE neutralizing antibody (P<0.05). CONCLUSION: 
      MRP8/MRP14 can induce the expression of TNF-alpha, IP-10 and IL-6 in mouse peritoneal 
      macrophages. MRP14 protein, which contain calcium binding motifs, has the 
      biological activity of inducing cytokine expression. TNF-alpha and IP-10 expressions 
      are related with TLR4 and its downstream p38 MAPKs and JNK; IL-6 is regulated by 
      both TLR4 and RAGE and their downstream p38 MAPKs and ERK.
FAU - Wang, Juan
AU  - Wang J
AD  - Department of Pathophysiology and Key Laboratory of Functional Proteomics of 
      Guangdong Province, Southern Medical University, Guangzhou 510515, China.E-mail: 
      w.juan601@163.com.
FAU - Li, Lei
AU  - Li L
FAU - Luo, Hai-Hua
AU  - Luo HH
FAU - Jiang, Yong
AU  - Jiang Y
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Nan Fang Yi Ke Da Xue Xue Bao
JT  - Nan fang yi ke da xue xue bao = Journal of Southern Medical University
JID - 101266132
PMC - PMC6765494
EDAT- 2017/09/28 06:00
MHDA- 2017/09/28 06:01
PMCR- 2017/09/20
CRDT- 2017/09/28 06:00
PHST- 2017/09/28 06:00 [entrez]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2017/09/28 06:01 [medline]
PHST- 2017/09/20 00:00 [pmc-release]
AID - nfykdxxb-37-9-1164 [pii]
AID - 10.3969/j.issn.1673-4254.2017.09.04 [doi]
PST - ppublish
SO  - Nan Fang Yi Ke Da Xue Xue Bao. 2017 Sep 20;37(9):1164-1170. doi: 
      10.3969/j.issn.1673-4254.2017.09.04.