Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P05231 (
interleukin-6
)
23,907
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments. Pharmacological inhibition of AMP-activated protein kinase reduced but did not prevent metformin-induced therapeutic effect as well as treatment of colitic mice with a pharmacological activator of AMP-activated protein kinase attenuated but did not resolve colitis. These data suggest that the anti-inflammatory effect of metformin relies on the control of additional pathways other than AMP-activated protein kinase. Indeed, metformin down-regulated
p38 MAP kinase
activation in colitic mice through an AMP-activated protein kinase-independent mechanism. Expression of active form of AMP-activated protein kinase was reduced in inflammatory bowel disease patients and treatment of mucosal cells of such patients with metformin enhanced AMP-activated protein kinase activation and reduced
p38 MAP kinase
activation, thereby inhibiting
interleukin-6
expression. Our findings indicate that metformin is a good candidate for inhibiting pathological inflammation in the gut.
...
PMID:Metformin inhibits inflammatory signals in the gut by controlling AMPK and p38 MAP kinase activation. 2954 May 37
Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is currently recommended as a useful medicine to chronic pain including low back pain. However, as the analogy of classical selective serotonin reuptake inhibitors, there is a concern to deteriorate osteoporosis with remaining to clarify the exact mechanism of duloxetine in bone metabolism. We have previously reported that prostaglandin E
1
(PGE
1
) induces the synthesis of both osteoprotegerin (OPG) and
interleukin-6
(
IL-6
), essential regulators of bone metabolism, in osteoblast-like MC3T3-E1 cells. Based upon them, we herein investigated the mechanism whereby the effect of duloxetine on the synthesis of OPG and
IL-6
induced by PGE
1
in these cells. Duloxetine enhanced the release from MC3T3-E1 cells of both OPG and
IL-6
stimulated by PGE
1
. However, reboxetine, a selective and specific inhibitor of norepinephrine reuptake, failed to affect the PGE
1
-induced release of OPG or
IL-6
. Oppositely, fluvoxamine and sertraline, agents belonging to the class of selective serotonin reuptake inhibitor, upregulated the PGE
1
-stimulated release of both OPG and
IL-6
. Duloxetine amplified the expression of OPG mRNA and
IL-6
mRNA stimulated by PGE
1
. Duloxetine strengthened the PGE
1
-induced
p38 MAP kinase
phosphorylation, which was amplified by fluvoxamine as well. SB203880, an inhibitor of
p38 MAP kinase
, suppressed the amplifying effects by duloxetine or fluvoxamine on the PGE
1
-stimulated release of OPG and
IL-6
. These results strongly suggest that duloxetine could strengthen osteoblast activation by PGE
1
through the upregulation of
p38 MAP kinase
, leading to increasing the synthesis of OPG and
IL-6
.
...
PMID:Duloxetine strengthens osteoblast activation by prostaglandin E
1
: Upregulation of p38 MAP kinase. 3300 95
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