PMID- 28791341
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20180515
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 40
IP  - 4
DP  - 2017 Oct
TI  - Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by 
      exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 
      suppression.
PG  - 1294-1301
LID - 10.3892/ijmm.2017.3090 [doi]
AB  - Renal failure is observed in the pathological progression of sepsis and septic 
      shock. Renal mesangial cells (RMCs) have been implicated in renal failure as a 
      result of producing mediators, such as monocyte chemoattractant protein-1 (MCP-1) 
      in response to lipopolysaccharide (LPS). Mitogen-activated protein kinases 
      (MAPKs) have been demonstrated to mediate the LPS-induced inflammatory response 
      in RMCs. Although previous studies indicated a promising effect of apocynin in 
      various inflammatory conditions, its antiseptic efficacy in mesangial cells 
      remains to be clearly determined. In the present study, the anti-inflammatory 
      effects of apocynin and its underlying mechanism were examined in LPS-challenged 
      RMCs. Apocynin significantly inhibited nitric oxide (NO) production in 
      LPS-challenged RMCs and the expression levels of inducible NO synthase and 
      cyclooxygenase-2. In addition, the level of LPS-induced MCP-1 expression was 
      significantly attenuated with apocynin. Furthermore, apocynin significantly 
      suppressed the activation of MAPKs, such as extracellular signal-regulated 
      kinases 1/2 and p38, but not c-Jun N-terminal kinases. Apocynin exhibited 
      significantly increased expression of heme oxygenase-1 (HO-1) induction via 
      nuclear factor (erythroid-derived 2)-like-2 (Nrf-2) phosphorylation. Inhibition 
      of HO-1 with zinc protoporphyrin significantly abolished apocynin-induced 
      suppression of MCP-1, indicating that HO-1 is significant in the suppression of 
      MCP-1. Thus, apocynin exerts antiseptic activity via the suppression of 
      pro-inflammatory signaling pathways and the activation of cytoprotective 
      signaling pathways, such as HO-1/Nrf-2 in RMCs, indicating that apocynin may 
      present as a promising candidate for in vivo evaluation of a therapeutic agent 
      for inflammation-associated renal disorders.
FAU - Bhatt, Nirmal Prasad
AU  - Bhatt NP
AD  - Department of Pharmacology, College of Medicine, Kangwon National University, 
      Chuncheon, Gangwon 200-701, Republic of Korea.
FAU - Park, Jin-Young
AU  - Park JY
AD  - Department of Pharmacology, College of Medicine, Kangwon National University, 
      Chuncheon, Gangwon 200-701, Republic of Korea.
FAU - Lee, Hee Jae
AU  - Lee HJ
AD  - Department of Pharmacology, College of Medicine, Kangwon National University, 
      Chuncheon, Gangwon 200-701, Republic of Korea.
FAU - Kim, Sung-Soo
AU  - Kim SS
AD  - Department of Pharmacology, College of Medicine, Kangwon National University, 
      Chuncheon, Gangwon 200-701, Republic of Korea.
FAU - Kwon, Yong-Soo
AU  - Kwon YS
AD  - College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 200-701, 
      Republic of Korea.
FAU - Chun, Wanjoo
AU  - Chun W
AD  - Department of Pharmacology, College of Medicine, Kangwon National University, 
      Chuncheon, Gangwon 200-701, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20170804
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Acetophenones)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Protoporphyrins)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - B6J7B9UDTR (acetovanillone)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acetophenones/antagonists & inhibitors/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/antagonists & inhibitors/*genetics/metabolism
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Heme Oxygenase-1/antagonists & inhibitors/*genetics/metabolism
MH  - Inflammation/prevention & control
MH  - Lipopolysaccharides/*antagonists & inhibitors/pharmacology
MH  - Mesangial Cells/cytology/*drug effects/metabolism
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Protoporphyrins/pharmacology
MH  - Rats
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
EDAT- 2017/08/10 06:00
MHDA- 2018/05/16 06:00
CRDT- 2017/08/10 06:00
PHST- 2017/03/21 00:00 [received]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/08/10 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/08/10 06:00 [entrez]
AID - 10.3892/ijmm.2017.3090 [doi]
PST - ppublish
SO  - Int J Mol Med. 2017 Oct;40(4):1294-1301. doi: 10.3892/ijmm.2017.3090. Epub 2017 
      Aug 4.