+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Down-regulation of mitogen-activated protein kinases and nuclear factor-κB signaling is involved in rapamycin suppression of TLR2-induced inflammatory response in monocytic THP-1 cells



Down-regulation of mitogen-activated protein kinases and nuclear factor-κB signaling is involved in rapamycin suppression of TLR2-induced inflammatory response in monocytic THP-1 cells



Microbiology and Immunology 59(10): 614-622



Tripalmitoyl-S-glycero-Cys-(Lys) 4 (Pam3CSK4) interacted with TLR2 induces inflammatory responses through the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signal pathway. Rapamycin can suppress TLR-induced inflammatory responses; however, the detailed molecular mechanism is not fully understood. Here, the mechanism by which rapamycin suppresses TLR2-induced inflammatory responses was investigated. It was found that Pam3CSK4-induced pro-inflammatory cytokines were significantly down-regulated at both the mRNA and protein levels in THP-1 cells pre-treated with various concentrations of rapamycin. Inhibition of phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) signaling did not suppress the expression of pro-inflammatory cytokines, indicating that the immunosuppression mediated by rapamycin in THP1 cells is independent of the PI3K/AKT pathway. RT-PCR showed that Erk and NF-κB signal pathways are related to the production of pro-inflammatory cytokines. Inhibition of Erk or NF-κB signaling significantly down-regulated production of pro-inflammatory cytokines. Additionally, western blot showed that pre-treatment of THP-1 cells with rapamycin down-regulates MAPKs and NF-κB signaling induced by Pam3CSK4 stimulation, suggesting that rapamycin suppresses Pam3CSK4-induced pro-inflammatory cytokines via inhibition of TLR2 signaling. It was concluded that rapamycin suppresses TLR2-induced inflammatory responses by down-regulation of Erk and NF-κB signaling.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057659733

Download citation: RISBibTeXText

PMID: 26337526

DOI: 10.1111/1348-0421.12321


Related references

Anti-inflammatory effect of Sosihotang via inhibition of nuclear factor-κB and mitogen-activated protein kinases signaling pathways in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Food and Chemical Toxicology 53: 343-351, 2013

Matrine induces cell anergy in human Jurkat T cells through modulation of mitogen-activated protein kinases and nuclear factor of activated T-cells signaling with concomitant up-regulation of anergy-associated genes expression. Biological and Pharmaceutical Bulletin 33(1): 40-46, 2010

Anti-inflammatory effects of (Z)-ligustilide through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways. Archives of Pharmacal Research 35(4): 723-732, 2012

The aqueous extract of Radix Glycyrrhizae stimulates mitogen-activated protein kinases and nuclear factor-kappaB in Jurkat T-cells and THP-1 monocytic cells. American Journal of Chinese Medicine 34(2): 263-278, 2006

Toluhydroquinone from Aspergillus sp. suppress inflammatory mediators via nuclear factor-κB and mitogen-activated protein kinases pathways in lipopolysaccharide-induced RAW264.7 cells. Journal of Pharmacy and Pharmacology 67(9): 1297-1305, 2015

Anti-inflammatory activities of Reynoutria elliptica through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways. Immunopharmacology and Immunotoxicology 34(3): 454-464, 2012

CD40-mediated signaling in monocytic cells: up-regulation of tumor necrosis factor receptor-associated factor mRNAs and activation of mitogen-activated protein kinase signaling pathways. International Immunology 13(3): 273-283, 2001

Xanthoceraside inhibits pro-inflammatory cytokine expression in Aβ25-35/IFN-γ-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor-κB, and mitogen-activated protein kinase signaling pathways. Journal of Pharmacological Sciences 122(4): 305-317, 2013

Luteolin is a bioflavonoid that attenuates adipocyte-derived inflammatory responses via suppression of nuclear factor-κB/mitogen-activated protein kinases pathway. Pharmacognosy Magazine 11(43): 627-635, 2015

Anti-Inflammatory activity of Angelica keiskei through suppression of mitogen-activated protein kinases and nuclear factor-kappaB activation pathways. Journal of Medicinal Food 13(3): 691-699, 2010

Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-kappaB. Journal of Neuroscience Research 86(13): 2932-2942, 2008

Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells. Journal of Biological Chemistry 269(5): 3731-3738, 1994

Polygoni Rhizoma inhibits inflammatory response through inactivation of nuclear factor-kappaB and mitogen activated protein kinase signaling pathways in RAW264.7 mouse macrophage cells. PhytoTherapy Research 26(2): 239-245, 2012