Lysophosphatidic Acid Induces Interleukin-13 (IL-13) Receptor α2 Expression and Inhibits IL-13 Signaling in Primary Human Bronchial Epithelial Cells

Zhao, Yutong; He, Donghong; Zhao, Jing; Wang, Lixin; Leff, Alan R.; Spannhake, E. W.; Georas, Steve N.; Natarajan, Viswanathan

doi:10.1074/jbc.m611210200

Cited by 43 publications

(60 citation statements)

References 57 publications

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“…We have previously shown transactivation of RTKs, such as PDGF-Rβ and EGF-R, by LPARs in HBEpCs [19,20]. Here we examined the cross-talk between LPA-Rs and c-Met in HBEpCs.…”

Section: Lpa Induces Serine Phosphorylation Of C-met Via G I and Pkc mentioning

confidence: 90%

“…The IL-8 expression is also partly regulated by protein kinase C δ (PKC δ), Nuclear factor-κB (NF-κB), and c-Jun-N-terminal Kinase (JNK)/AP-1 transcriptional factors [16][17][18]. Furthermore, LPA induced IL-13 receptor alpha2 (IL-13Rα2) expression and secretion and attenuated IL-13-induced signaling in HBEpCs [19]. In addition, ligation of LPA to LPA-Rs transactivated RTKs, such as Platelet-Derived Growth Factor Receptor beta (PDGF-Rβ) [20] and Epidermal Growth Factor Receptor (EGF-R) [21].…”

Section: Introductionmentioning

confidence: 99%

“…EGF-R transactivation by LPA contributed to LPAinduced IL-8 secretion [21], while PDGF-Rβ transactivation was involved in LPA-induced phosphorylation of extracelluar signal-regulated kinase (Erk) [20]. LPA also induced PDGF-Rβ transactivation through phospholipase D 2 (PLD2) [19] and EGF-R transactivation through PKC δ-mediated activation of lyn kinase, matrix metallopreinases, and heparin-binding EGF (HB-EGF) shedding in HBEpCs [21].…”

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

Zhao¹,

He²,

Stern³

et al. 2007

Cellular Signalling

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Previously we demonstrated that ligation of lysophosphatidic acid (LPA) to G protein-coupled LPA receptors induces transactivation of receptor tyrosine kinases (RTKs), such as platelet-derived growth factor receptor beta (PDGF-Rβ) and epidermal growth factor receptor (EGF-R), in primary cultures of human bronchial epithelial cells (HBEpCs). Here we examined the role of LPA on c-Met redistribution and modulation of hepatocyte growth factor ( These results demonstrate that LPA regulates c-Met function through PKC δ-and E-cadherin in HBEpCs, suggesting an alternate function of the cross-talk between G-protein coupled receptors (GPCRs) and RTKs in HBEpCs.

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“…We have previously shown transactivation of RTKs, such as PDGF-Rβ and EGF-R, by LPARs in HBEpCs [19,20]. Here we examined the cross-talk between LPA-Rs and c-Met in HBEpCs.…”

Section: Lpa Induces Serine Phosphorylation Of C-met Via G I and Pkc mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

Zhao¹,

He²,

Stern³

et al. 2007

Cellular Signalling

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“…Indeed, overexpression of IL-13R␣2 diminished IL-13 signaling (17,18) and treatment with an IL-13R␣2-Fc fusion protein prevented IL-13-induced liver fibrosis in a mouse model of schistosomiasis (19,20). It was also reported that lysophosphatidic acid was able to inhibit IL-13 signaling in vitro via up-regulation of IL-13R␣2 (21). However, a recent report has questioned this concept.…”

Section: T He Cytokines Il-4 and Il-13 Are Important Mediators Ofmentioning

confidence: 99%

IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung

Zheng

Liu²,

et al. 2008

The Journal of Immunology

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IL-13 is a critical cytokine at sites of Th2 inflammation. In these locations it mediates its effects via a receptor complex, which contains IL-4Rα and IL-13Rα1. A third, high-affinity IL-13 receptor, IL-13Rα2, also exists. Although it was initially felt to be a decoy receptor, this has not been formally demonstrated and the role(s) of this receptor has recently become controversial. To define the role(s) of IL-13Rα2 in IL-13-induced pulmonary inflammation and remodeling, we compared the effects of lung-targeted transgenic IL-13 in mice with wild-type and null IL-13Rα2 loci. We also investigated the effect of IL-13Rα2 deficiency on the OVA-induced inflammatory response. In this study, we show that in the absence of IL-13Rα2, IL-13-induced pulmonary inflammation, mucus metaplasia, subepithelial fibrosis, and airway remodeling are significantly augmented. These changes were accompanied by increased expression and production of chemokines, proteases, mucin genes, and TGF-β1. Similarly, an enhanced inflammatory response was observed in an OVA-induced phenotype. In contrast, disruption of IL-13Rα2 had no effect on the tissue effects of lung-targeted transgenic IL-4. Thus, IL-13Rα2 is a selective and powerful inhibitor of IL-13-induced inflammatory, remodeling, and physiologic responses in the murine lung.

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“…It is tempting to speculate that activation of the σ E response and the resulting suppression of multiple outer membrane proteins might represent another immune evasion strategy of Salmonella. Moreover, this type of adaptation seems predominantly important inside monocytes, which express a wide range of cytosolic PRRs (Takeshita et al, 2004;Zhao et al, 2007).…”

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confidence: 99%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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Lysophosphatidic Acid Induces Interleukin-13 (IL-13) Receptor α2 Expression and Inhibits IL-13 Signaling in Primary Human Bronchial Epithelial Cells

Cited by 43 publications

References 57 publications

Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung

Dual RNA-seq of pathogen and host

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