TLR2/1 and sphingosine 1-phosphate modulate inflammation, myofibroblast differentiation and cell migration in fibroblasts

Hamidi, Saghi; Schäfer‐Korting, Monika; Weindl, Günther

doi:10.1016/j.bbalip.2014.01.008

Cited by 35 publications

(29 citation statements)

References 55 publications

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“…LPS during the acute activation of TLR2 signaling [27], further demonstrating the expression of TLR2 in fibroblasts [13, 14]. In contrast, the mRNA expressions of both collagens III and IV in fibroblasts were significantly decreased at 24 and 48 h (the late culture periods) after challenge with P.g.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptors (TLRs), which are expressed in fibroblasts [13, 14], have been observed to modulate tissue repair during chronic inflammation [15–17]. Furthermore, nuclear factor kappa B (NF- κ B), the key transcription factor of TLR signaling, has been shown to inhibit collagen I gene expression directly [18] and mediate oxidative stress-decreased collagen biosynthesis [19].…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF‐κB Activation

et al. 2016

Oxidative Medicine and Cellular Longevity

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Fibroblasts are essential for tissue repair due to producing collagens, and lysosomal proteinase cathepsin B (CatB) is involved in promoting chronic inflammation. We herein report that CatB regulates the expression of collagens III and IV by fibroblasts in response to a TLR2 agonist, lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). In cultured human BJ fibroblasts, mRNA expression of CatB was significantly increased, while that of collagens III and IV was significantly decreased at 24 h after challenge with P.g. LPS (1 μg/mL). The P.g. LPS-decreased collagen expression was completely inhibited by CA-074Me, the specific inhibitor of CatB. Surprisingly, expression of collagens III and IV was significantly increased in the primary fibroblasts from CatB-deficient mice after challenge with P.g. LPS. The increase of CatB was accompanied with an increase of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and a decrease of IκBα. Furthermore, the P.g. LPS-increased 8-OHdG and decreased IκBα were restored by CA-074Me. Moreover, 87% of CatB and 86% of 8-OHdG were colocalized with gingival fibroblasts of chronic periodontitis patients. The findings indicate the critical role of CatB in regulating the expression of collagens III and IV by fibroblasts via prolonging TLR2/NF-κB activation and oxidative stress. CatB-specific inhibitors may therefore improve chronic inflammation-delayed tissue repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF‐κB Activation

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…After stimulation, MoLC were washed with PBS and lysed, according to a previously described protocol (19). Samples containing 25 mg protein (Pierce BCA Protein Assay; Thermo Scientific) were boiled in standard SDS-PAGE sample buffer in the presence of DTT and separated by 10% SDS-PAGE (Bio-Rad, Munich, Germany).…”

Section: Western Blottingmentioning

confidence: 99%

Chloroquine Promotes IL-17 Production by CD4+ T Cells via p38-Dependent IL-23 Release by Monocyte-Derived Langerhans-like Cells

Said

Bock

Lajqi

et al. 2014

The Journal of Immunology

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Recent studies suggest a role for autophagy in the secretion of IL-1 cytokines regulating the development of inflammatory diseases. The antimalarial drug and autophagy/lysosome inhibitor chloroquine (CHQ) is considered as potential trigger of drug-induced or drug-aggravated psoriasis, in which Th17 cells sustain a persistent inflammation. In this study, we investigated the effect of CHQ on human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in response to IL-1β. The presence of CHQ reduced IL-12p70 release in both subsets, but surprisingly increased IL-6 production in MoDC and IL-23 in MoLC. Importantly, CHQ-treated MoLC promoted IL-17A secretion by CD4+ T cells and elevated RORC mRNA levels, whereas IFN-γ release was reduced. The dysregulation of IL-12 family cytokines in MoLC and MoDC occurred at the transcriptional level. Similar effects were obtained with other late autophagy inhibitors, whereas PI3K inhibitor 3-methyladenine failed to increase IL-23 secretion. The modulated cytokine release was dependent on IL-1 cytokine activation and abrogated by a specific IL-1R antagonist. CHQ elevated expression of TNFR-associated factor 6, a common intermediate in IL-1R and TLR-dependent signaling. Accordingly, treatment with Pam3CSK4 and CHQ enhanced IL-23 release in MoLC and MoDC. CHQ inhibited autophagic flux, confirmed by increased LC3-II and p62 expression, and activated ERK, p38, and JNK MAPK, but only inhibition of p38 abrogated IL-23 release by MoLC. Thus, our findings indicate that CHQ modulates cytokine release in a p38-dependent manner, suggesting an essential role of Langerhans cells and dendritic cells in CHQ-provoked psoriasis, possibly by promoting Th17 immunity.

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“…In skin fibroblasts and normal rat kidney interstitial fibroblast cells, S1P stimulation enhanced differentiation to myofibroblasts and induction of ECM protein expression. 30,52,53 S1P also increased collagen expression by hepatic myofibroblasts. 36 Previous studies examined the effect of S1P on ocular tissue.…”

Section: Discussionmentioning

confidence: 92%

Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma

Aoyama-Araki

Honjo

Uchida

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Aoyama-Araki Y, Honjo M, Uchida T, et al. Sphingosine-1-phosphate (S1P)-related response of human conjunctival fibroblasts after filtration surgery for glaucoma. Invest Ophthalmol Vis Sci. 2017;58:225858: -226558: . DOI:10.1167 PURPOSE. To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid samples taken before and after filtration surgery and S1P-induced human conjunctival fibroblast (HCF) responses.METHODS. Levels of S1P and its related sphingophospholipids in aqueous fluid obtained immediately before and after filtration surgery were determined by liquid chromatographytandem mass spectrometry. HCFs were used for all in vitro experiments. The expression of five S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The effect of S1P and receptor-specific antagonists on HCF viability and cell migration was assessed by WST-1 assay and scratch migration assay, respectively. Differentiation to myofibroblasts and extracellular matrix production was evaluated by examining changes in F-actin, a-smooth muscle actin (aSMA), and collagen expression with immunocytochemistry, Western blotting, and collagen accumulation assay, respectively. RESULTS.No significant S1P levels in the aqueous fluid samples were detectable immediately before surgery, but postoperative levels of several lysophospholipids, including S1P, dehydro-S1P, and sphingosine, were significantly increased to bioactive concentrations in aqueous fluid in the blebs (P < 0.0001). mRNA expression of the three main S1P receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2 antagonist JTE 013. F-actin, aSMA, and collagen expression was significantly increased by S1P stimulation and was reduced by JTE 013.CONCLUSIONS. Bioactive S1P concentrations were present in the aqueous fluid at the end of filtration surgery. S1P activated HCFs via S1P2 receptors. These results revealed the potential of S1P2 antagonists in preventing scarring after glaucoma filtration surgery.

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TLR2/1 and sphingosine 1-phosphate modulate inflammation, myofibroblast differentiation and cell migration in fibroblasts

Cited by 35 publications

References 55 publications

Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF‐κB Activation

Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF‐κB Activation

Chloroquine Promotes IL-17 Production by CD4+ T Cells via p38-Dependent IL-23 Release by Monocyte-Derived Langerhans-like Cells

Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma

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