Heparin inhibits melanosome uptake and inflammatory response coupled with phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways in human epidermal keratinocytes

2014 ◽  
Vol 27 (6) ◽  
pp. 1063-1074 ◽  
Author(s):  
Chieko Makino-Okamura ◽  
Yoko Niki ◽  
Seiji Takeuchi ◽  
Chikako Nishigori ◽  
Lieve Declercq ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Erk Signaling ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Xudong Pu ◽  
Xin Li ◽  
Lili Cao ◽  
Kaiming Yue ◽  
Panpan Zhao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Proinflammatory Cytokines ◽  
Giardia Duodenalis ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Mouse Macrophages ◽  
Host Inflammatory Response

Giardia duodenalis, also known as Giardia lamblia or Giardia intestinalis, is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis–stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis–induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis.

Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes

Inflammation ◽  
2013 ◽  
Vol 36 (6) ◽  
pp. 1316-1326 ◽  
Author(s):  
Iole Paoletti ◽  
Vincenza De Gregorio ◽  
Adone Baroni ◽  
Maria Antonietta Tufano ◽  
Giovanna Donnarumma ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Ifn Γ

scholarly journals Deducing signaling pathways from parallel actions of arsenite and antimonite in human epidermal keratinocytes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marjorie A. Phillips ◽  
Angela Cánovas ◽  
Miguel A. Rea ◽  
Alma Islas-Trejo ◽  
Juan F. Medrano ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yaxi Wu ◽  
Jinshan Ye ◽  
Ruiwei Guo ◽  
Xing Liang ◽  
Lixia Yang
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Erk Signaling ◽  
Oxidized Low Density Lipoprotein ◽  
Inflammatory Signaling ◽  
Raw264.7 Macrophages ◽  
Novel Therapeutic

Toll/IL-1R-domain-containing adaptor-inducing IFN-β (TRIF) is an important adaptor for TLR3- and TLR4-mediated inflammatory signaling pathways. Recent studies have shown that TRIF plays a key role in vessel inflammation and atherosclerosis; however, the precise mechanisms are unclear. We investigated the mechanisms of the TRIF-regulated inflammatory response in RAW264.7 macrophages under oxidized low-density lipoprotein (ox-LDL) stimulation. Our data show that ox-LDL induces TRIF, miR-155, and BIC expression, activates the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways, and elevates the levels of IL-6 and TNF-α in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-α expression and inhibited the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways. Inhibition of ERK1/2 signaling also suppressed BIC and miR-155 expression. These findings suggest that TRIF plays an important role in regulating the ox-LDL-induced macrophage inflammatory response and that TRIF modulates the expression of BIC/miR-155 and the downstream SOCS1-STAT3-NF-κB signaling pathway via ERK1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.

Leptin regulates the pro-inflammatory response in human epidermal keratinocytes

2018 ◽  
Vol 310 (4) ◽  
pp. 351-362 ◽  
Author(s):  
Moonyoung Lee ◽  
Eunyoung Lee ◽  
Sun Hee Jin ◽  
Sungjin Ahn ◽  
Sae On Kim ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Psoriasis-Associated Inflammatory Conditions Induce IL-23 mRNA Expression in Normal Human Epidermal Keratinocytes

2022 ◽  
Vol 23 (1) ◽  
pp. 540
Author(s):  
Evelyn Kelemen ◽  
Éva Ádám ◽  
Stella Márta Sági ◽  
Anikó Göblös ◽  
Lajos Kemény ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Poly I:C ◽  
Psoriatic Skin ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Normal Human Epidermal Keratinocytes ◽  
Normal Human

Psoriasis is a multifactorial, chronic inflammatory skin disease, the development of which is affected by both genetic and environmental factors. Cytosolic nucleic acid fragments, recognized as pathogen- and danger-associated molecular patterns, are highly abundant in psoriatic skin. It is known that psoriatic skin exhibits increased levels of IL-23 compared to healthy skin. However, the relationship between free nucleic acid levels and IL-23 expression has not been clarified yet. To examine a molecular mechanism by which nucleic acids potentially modulate IL-23 levels, an in vitro system was developed to investigate the IL-23 mRNA expression of normal human epidermal keratinocytes under psoriasis-like circumstances. This system was established using synthetic nucleic acid analogues (poly(dA:dT) and poly(I:C)). Signaling pathways, receptor involvement and the effect of PRINS, a long non-coding RNA previously identified and characterized by our research group, were analyzed to better understand the regulation of IL-23 in keratinocytes. Our results indicate that free nucleic acids regulate epithelial IL-23 mRNA expression through the TLR3 receptor and specific signaling pathways, thereby, contributing to the development of an inflammatory milieu favorable for the appearance of psoriatic symptoms. A moderate negative correlation was confirmed between the nucleic-acid-induced IL-23 mRNA level and the rate of its decrease upon PRINS overexpression.

Sign in / Sign up

Export Citation Format

Share Document