scholarly journals Aryl Hydrocarbon Receptor Modulates the Expression of TNF-α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways

2018 ◽  
Vol 11 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Xiao-Xiao Hou ◽  
Guangjie Chen ◽  
Amir M. Hossini ◽  
Tingting Hu ◽  
Lanqi Wang ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Physiological Stress ◽  
Acne Vulgaris ◽  
Receptor Protein ◽  
Inflammatory Factors ◽  
Induced Expression ◽  
Aryl Hydrocarbon ◽  
Tnf Α ◽  
P38mapk Signaling ◽  
Myeloid Differentiation Factor

Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF-α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-κB in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-α and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-κB/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne.

scholarly journals Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88

2020 ◽  
pp. 175342592092747
Author(s):  
Yajie Yang ◽  
Yan Hu ◽  
Yile Zhou ◽  
Tao Liang ◽  
Haihong Tang ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Myeloid Differentiation ◽  
Study Group ◽  
Tlr4 Expression ◽  
Wild Type ◽  
Human Embryonic Kidney ◽  
Gram Negative ◽  
Tnf Α ◽  
Polymorphic Variants ◽  
Myeloid Differentiation Factor

TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.

scholarly journals Role of the Aryl Hydrocarbon Receptor in the Immune Response Profile and Development of Pathology during Plasmodium berghei Anka Infection

2014 ◽  
Vol 82 (8) ◽  
pp. 3127-3140 ◽  
Author(s):  
Fatima Brant ◽  
Aline S. Miranda ◽  
Lisia Esper ◽  
David Henrique Rodrigues ◽  
Lucas Miranda Kangussu ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Plasmodium Berghei ◽  
Transforming Growth Factor ◽  
Interleukin 17 ◽  
High Morbidity ◽  
Content Type ◽  
Aryl Hydrocarbon ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Brain

ABSTRACTInfection withPlasmodium falciparummay result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality.Plasmodium bergheiAnka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected withP. bergheiAnka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1β, and IFN-γ, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, andP. bergheiAnka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria.

Silencing of aryl hydrocarbon receptor protein (AIP) up-regulates the small Rho GTPase, CDC42

2015 ◽  
Author(s):  
Nadira B Mothojakan ◽  
Craig E Stiles ◽  
Sayka Barry ◽  
Carol C Shoulders ◽  
Marta Korbonits
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Rho Gtpase ◽  
Receptor Protein ◽  
Aryl Hydrocarbon

scholarly journals Indoxyl sulfate–induced TNF‐α is regulated by crosstalk between the aryl hydrocarbon receptor, NF‐κB, and SOCS2 in human macrophages

2019 ◽  
Vol 33 (10) ◽  
pp. 10844-10858 ◽  
Author(s):  
Hee Young Kim ◽  
Tae-Hyun Yoo ◽  
Joo-Youn Cho ◽  
Hyeon Chang Kim ◽  
Won-Woo Lee
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Indoxyl Sulfate ◽  
Human Macrophages ◽  
Aryl Hydrocarbon ◽  
Tnf Α

scholarly journals Role of NF-kB RelB in Aryl Hydrocarbon Receptor-Mediated Ligand Specific Effects

2019 ◽  
Vol 20 (11) ◽  
pp. 2652 ◽  
Author(s):  
Yasuhiro Ishihara ◽  
Sarah Y. Kado ◽  
Christiane Hoeper ◽  
Shelly Harel ◽  
Christoph F. A. Vogel
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Functional Expression ◽  
Dependent Manner ◽  
Induced Expression ◽  
Aryl Hydrocarbon ◽  
Regulatory Enzymes ◽  
Basal Expression ◽  
Expression Of Genes ◽  
Ahr Gene

Here, we investigate the role of RelB in the regulation of genes which were identified to be induced in an aryl hydrocarbon receptor (AhR)-dependent manner and critically involved in regulation of immune responses. We analyzed the expression of genes of the AhR gene battery, cytokines, and immune regulatory enzymes in bone marrow-derived macrophages (BMM) and thymus of B6 wildtype (wt) mice and RelB knockout (RelB−/−) mice after treatment with various AhR ligands. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced expression of indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2 was significantly repressed in thymus of RelB−/− mice but not in BMM derived from RelB−/− mice. Interestingly, the induced and basal expression of the cytokines interleukin (IL)-17A, IL-22, and CCL20 required the functional expression of RelB. The RelB-dependent expression of CCL20 was induced by the AhR ligands TCDD and 6-formylindolo[3,2-b]carbazole (FICZ), whereas indole-3-carbinol (I3C) suppressed CCL20 in lipopolysaccharide (LPS)-activated wt BMM. The LPS-induced expression of IL-6 and IL-10 was enhanced by TCDD and FICZ, whereas I3C significantly suppressed these cytokines in BMM. The exposure to FICZ led to higher increases of IL-17A and IL-22 mRNA compared to the effect of TCDD or I3C in thymus of wt mice. On the other hand, TCDD was the strongest inducer of CYP1A1, AhR Repressor (AhRR), and IDO2. In summary, these findings provide evidence for the important role of RelB in the transcriptional regulation of cytokines and enzymes induced by AhR ligands.

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