PMID- 27173611
OWN - NLM
STAT- MEDLINE
DCOM- 20170302
LR  - 20181113
IS  - 1543-706X (Electronic)
IS  - 1071-2690 (Linking)
VI  - 52
IP  - 8
DP  - 2016 Sep
TI  - ROCK activity affects IL-1-induced signaling possibly through MKK4 and p38 MAPK 
      in Caco-2 cells.
PG  - 878-84
LID - 10.1007/s11626-016-0050-0 [doi]
AB  - Elevated levels of interleukin-1 (IL-1) accompany inflammatory bowel disease. 
      IL-1-stimulated intestinal epithelial cells can secrete potent chemokines like 
      CXCL8 to exacerbate inflammation. Previously, we found that inhibiting the 
      Rho-associated kinase (ROCK) could inhibit IL-1- or TNF-alpha-induced CXCL8 secretion 
      by the Caco-2 colonic epithelial cell line. This ROCK inhibition did not affect 
      IkappaBalpha phosphorylation and degradation, but suppressed the phosphorylation of c-Jun 
      N-terminal kinase (JNK). Therefore, ROCK must play an important role in 
      epithelial cell CXCL8 responses through an effect on the JNK signaling pathway. 
      Here, we extend these studies by showing that inhibiting ROCK suppressed the 
      IL-1-induced phosphorylation of MKK4, a known activator of JNK, but not MKK7. 
      Yet, ROCK inhibition had no significant effect on the IL-1-induced 
      phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2. Inhibiting 
      ROCK also suppressed the phosphorylation of p38 MAPK after IL-1 stimulation, but 
      this inhibition had no significant effect on the stability of CXCL8 messenger RNA 
      (mRNA) after IL-1 stimulation. These results suggest that ROCK may be important 
      in IL-1-induced signaling through MKK4 to JNK and the activation of p38 MAPK. 
      Finally, inhibiting ROCK in IL-1 and TNF-alpha co-stimulated Caco-2 cells also 
      resulted in a significant suppression of CXCL8 secretion and mRNA levels 
      suggesting that inhibiting ROCK may be a mechanism to inhibit the overall 
      response of epithelial cells to both cytokines. These studies indicate a novel 
      signaling event, which could provide a target for suppressing intestinal 
      epithelial cells (IEC) chemokine responses involved in mucosal inflammation.
FAU - Banerjee, Sayantan
AU  - Banerjee S
AD  - Department of Biological Sciences, Binghamton University (SUNY), Binghamton, NY, 
      13902-6000, USA.
FAU - McGee, Dennis W
AU  - McGee DW
AD  - Department of Biological Sciences, Binghamton University (SUNY), Binghamton, NY, 
      13902-6000, USA. dmcgee@binghamton.edu.
LA  - eng
PT  - Journal Article
DEP - 20160512
PL  - Germany
TA  - In Vitro Cell Dev Biol Anim
JT  - In vitro cellular & developmental biology. Animal
JID - 9418515
RN  - 0 (Amides)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 7)
RN  - EC 2.7.12.2 (MAP2K4 protein, human)
RN  - EC 2.7.12.2 (MAP2K7 protein, human)
SB  - IM
MH  - Amides/administration & dosage
MH  - Caco-2 Cells
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Inflammation/*genetics/metabolism/pathology
MH  - Interleukin-1/*metabolism
MH  - Interleukin-8/biosynthesis/*genetics
MH  - MAP Kinase Kinase 4/*biosynthesis/genetics
MH  - MAP Kinase Kinase 7/biosynthesis/genetics
MH  - Phosphorylation/drug effects
MH  - Pyridines/administration & dosage
MH  - RNA, Messenger/biosynthesis
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*biosynthesis/genetics
MH  - rho-Associated Kinases/antagonists & inhibitors/biosynthesis/*genetics
OTO - NOTNLM
OT  - ERK
OT  - IL-1
OT  - MKK4
OT  - ROCK
OT  - p38 MAPK
EDAT- 2016/05/14 06:00
MHDA- 2017/03/03 06:00
CRDT- 2016/05/14 06:00
PHST- 2016/01/13 00:00 [received]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/05/14 06:00 [entrez]
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2017/03/03 06:00 [medline]
AID - 10.1007/s11626-016-0050-0 [pii]
AID - 10.1007/s11626-016-0050-0 [doi]
PST - ppublish
SO  - In Vitro Cell Dev Biol Anim. 2016 Sep;52(8):878-84. doi: 
      10.1007/s11626-016-0050-0. Epub 2016 May 12.