Cooperative molecular and cellular networks regulate Toll‐like receptor‐dependent inflammatory responses

Morris, George E.; Parker, Lisa C.; Ward, Julian; Whyte, Moira K. B.; Brightling, Christopher E.; Bradding, Peter; Dower, Steven K.; Sabroe, Ian

doi:10.1096/fj.06-5910fje

Cited by 73 publications

(128 citation statements)

References 55 publications

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“…Poly(I:C) also induced significant IL-8 release from HUVECs ( Fig. 2A, right panel), consistent with previous studies [15]. Dose titration of poly(I:C) with concentrations ranging from 1-100 μg/ml showed that approximately 25 μg/ml poly(I:C) resulted in maximal IL-8 release from SLK cells (data not shown), and this concentration was used in all subsequent experiments.…”

Section: Human Kaposi's Sarcoma Slk Cells Produce Il-8 In Response Tosupporting

confidence: 90%

Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line

Livengood¹,

Wu²,

Carson³

2007

Cellular Immunology

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Kaposi's sarcoma (KS) is strongly associated with KS herpes virus infection, and inflammation plays an important role in this disease. We have shown that human KS biopsy-derived SLK cells, which are of endothelial origin and form KS-like tumors in nude mice, express the viral RNA pattern recognition receptors Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (RIG-I), and melanoma-differentiation-associated gene 5 (MDA5). Furthermore, SLK cells have enhanced release of IL-6, IL-8 (CXCL8), RANTES (CCL5), and IP-10 (CXCL10) proteins in response to the synthetic viral RNA analog poly(I:C). SiRNA knockdowns demonstrated that TLR3 mediates this inflammatory response to poly(I:C) in SLK cells. Furthermore, knockdown of the RNA receptor RIG-I resulted in enhanced chemokine release, in a TLR3 pathway-dependent manner. Thus, exposure of KS cells to viral RNA ligands can result in a TLR3-mediated increase in the secretion of inflammatory proteins associated with KS cell growth that may contribute to disease.

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Section: Human Kaposi's Sarcoma Slk Cells Produce Il-8 In Response Tosupporting

confidence: 90%

Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line

Livengood¹,

Wu²,

Carson³

2007

Cellular Immunology

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“…Strikingly, TNF-␣ regulates the expression of TLRs, including TLR9, TLR5, and TLR22, in these cells but has negligible effects on macrophages. Similarly, mammalian endothelial cells are endowed with several TLRs, which allows them to cooperate with professional phagocytes in the recognition of microbes and the induction of inflammation (42,43). Interestingly, TNF-␣ and TLR ligands also substantially increased the expression of MHC class II and CD83 in endothelial cells, which might suggest a role for fish endothelial cells and TNF-␣ in Ag presentation.…”

Section: Discussionmentioning

confidence: 99%

Evolution of the Inflammatory Response in Vertebrates: Fish TNF-α Is a Powerful Activator of Endothelial Cells but Hardly Activates Phagocytes

Roca

Mulero

López-Muñoz

et al. 2008

The Journal of Immunology

187

106

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TNF-α is conserved in all vertebrate classes and has been identified in all taxonomic groups of teleost fish. However, its biological activities and its role in infection are largely unknown. Using two complementary fish models, gilthead seabream and zebrafish, we report here that the main proinflammatory effects of fish TNF-α are mediated through the activation of endothelial cells. Thus, TNF-α promotes the expression of E-selectin and different CC and CXC chemokines in endothelial cells, thus explaining the recruitment and activation of phagocytes observed in vivo in both species. We also found that TLR ligands, and to some extent TNF-α, were able to increase the expression of MHC class II and CD83 in endothelial cells, which might suggest a role for fish endothelial cells and TNF-α in Ag presentation. Lastly, we found that TNF-α increases the susceptibility of the zebrafish to viral (spring viremia of carp virus) and bacterial (Streptococcus iniae) infections. Although the powerful actions of fish TNF-α on endothelial cells suggest that it might facilitate pathogen dissemination, it was found that TNF-α increased antiviral genes and, more importantly, had little effect on the viral load in early infection. In addition, the stimulation of ZF4 cells with TNF-α resulted in increased viral replication. Together, these results indicate that fish TNF-α displays different sorts of bioactivity to their mammalian counterparts and point to the complexity of the evolution that has taken place in the regulation of innate immunity by cytokines.

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“…CXC chemokine receptor (CXCR)3 is the most abundantly expressed chemokine receptor on human lung mast cells within the ASM bundle. Human lung mast cell migration is induced by the CXCR3 ligand CXCL10, which is released preferentially from Th1-stimulated asthmatic ASM cells compared with those from healthy controls [140] and is released in response to Toll-like receptor-3 activation [141]. Interestingly, Th2-stimulated ASM from asthmatics is chemotactic for mast cells compared with nonasthmatic ASM mediated via activation of CCR3 and CXCR1.…”

Section: What Mechanisms Are Involved In Selective Localisation?mentioning

confidence: 99%

Inflammatory cell microlocalisation and airway dysfunction: cause and effect?

Siddiqui

Hollins²,

Saha³

et al. 2007

Eur Respir J

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Airway inflammation is a critical feature of the airway diseases asthma and chronic obstructive pulmonary disease (COPD). There is emerging evidence that structural cells play a key role in the development and perpetuation of the inflammatory response and are pivotal in the development of the changes in the airway structures that lead to airway remodelling.To date, little attention has been given to the localisation of inflammatory cells to airway structures or the potential interactions between these intimately located cells. However, it is likely that interactions between inflammatory and structural cells in the airway contribute enormously to the pathophysiology of asthma and COPD.Indeed, recent evidence suggests that mast cells localised to the airway smooth muscle bundle may be important in the development of airway hyperresponsiveness in asthma.In the present article, the authors aim to summarise: 1) the current understanding of which inflammatory cells locate to airway structures; 2) the proposed mechanisms that may be involved in mediating this microlocalisation; 3) the possible consequences of interactions between inflammatory and structural cells; and 4) the pressing need to investigate whether modulating these interactions is beneficial in asthma and chronic obstructive pulmonary disease.

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Cooperative molecular and cellular networks regulate Toll‐like receptor‐dependent inflammatory responses

Cited by 73 publications

References 55 publications

Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line

Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line

Evolution of the Inflammatory Response in Vertebrates: Fish TNF-α Is a Powerful Activator of Endothelial Cells but Hardly Activates Phagocytes

Inflammatory cell microlocalisation and airway dysfunction: cause and effect?

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