Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Bhattacharyya, Sumit; Dudeja, Pradeep K.; Tobacman, Joanne K.

doi:10.1152/ajpgi.90434.2008

Cited by 35 publications

(39 citation statements)

References 31 publications

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“…In both human colonic epithelial cells with a silenced BCL10 gene and the intestinal tissue of Bcl10 -/-mice, it has been shown that the TLR4 response is BCL10 dependent. However, other studies have shown that TLR4 signaling may follow both BCL10-dependent and -independent pathways (22)(23)(24)(25)(26). Although we did not test epithelial cells from P1, the results we obtained for fibroblasts were consistent with those of previous studies on epithelial cells (36), which indicates that the TLR4 response is BCL10 dependent and IKKB dependent in human fibroblasts.…”

Section: Resultssupporting

confidence: 88%

“…In fibroblasts, a heterotrimer consisting of CARD10 (also known as CARMA3), BCL10, and MALT1 forms. Many studies have on epithelial cells (such as human colonic epithelial cells) in which BCL10 was silenced, and in intestinal cells from Bcl10 -/-mice, have demonstrated that the TLR4 response is BCL10 dependent (22)(23)(24)(25)(26). We therefore analyzed the effect of BCL10 deficiency in primary fibroblasts from P1, which we compared with cells from healthy donors, by measuring the production of IL-6 and IL-8 in response to TLR4, TLR2/6, Dectin-1, and TLR3 stimulation ( Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

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Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Torres¹,

Martı́nez-Barricarte²,

García-Gómez³

et al. 2014

J. Clin. Invest.

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Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Torres¹,

Martı́nez-Barricarte²,

García-Gómez³

et al. 2014

J. Clin. Invest.

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“…In this report, we extend findings from our previous studies about how activation of canonical and noncanonical signaling of NF-B is mediated by BCL10 following stimulation by carrageenan (CGN) or lipopolysaccharide in human colonic epithelial cells (2)(3)(4)(5)(6)10). The sulfated polysaccharide CGN has been used for decades to induce inflammation in animal models to study mediators of inflammation and pharmacological agents that reduce inflammation.…”

supporting

confidence: 77%

Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-κB activation following carrageenan

Bhattacharyya

Borthakur

Anbazhagan

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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To determine the impact of B cell leukemia/lymphoma (BCL) 10 on the phosphorylation of crucial mediators in NF-B-mediated inflammatory pathways, human colonic epithelial cells were exposed to carrageenan (CGN), a sulfated polysaccharide commonly used as a food additive and known to induce NF-B nuclear translocation by both canonical and noncanonical pathways. Phosphorylations of intermediates in inflammatory cascades, including NF-B-inducing kinase (NIK) at Thr 559 , transforming growth factor-␤-activating kinase ( B cell leukemia/lymphoma; nuclear factor-B

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“…53 Absence of TLR-4 in HBEC challenged with media, LPS, IL-13, and supernatant from control or LPStreated MDM suggests that HBEC may have responded to LPS via a TLR-4-independent pathway like other epithelial cells do. 54 Moreover, a basolateral HBEC response to LPS could be a relevant defensive mechanism towards infiltrating pathogens, increasing airway mucus to prevent additional microbial invasion. HBEC stimulated with supernatant from control MDM result in a partial inhibition of MUC5B, and none of the cytokines tested could reproduce this effect.…”

Section: Discussionmentioning

confidence: 99%

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

Silva

Berčík

2012

Laboratory Investigation

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Airway goblet cell hyperplasia (GCH)-detectable by mucin staining-and abnormal macrophage infiltrate are pathological features present in many chronic respiratory disorders. However, it is unknown if both factors are associated. Using in-vivo and in-vitro models, we investigated whether macrophages are related with GCH and changes in mucin immunophenotypes. Lung sections from Sprague-Dawley rats treated for 48 h with one intra-tracheal dose of PBS or LPS (n ¼ 4-6 per group) were immunophenotyped for rat-goblet cells, immune, and proliferation markers. Human monocytederived macrophages (MDM) were pre-treated with or without LPS, immunophenotyped, and their supernatant, as well as cytokines at levels equivalent to supernatant were used to challenge primary culture of normal human bronchus epithelial cells (HBEC) in air-liquid interface, followed by MUC5B and MUC5AC mucin immunostaining. An association between increased bronchiolar goblet cells and terminal-bronchiolar proliferative epithelial cells confirmed the presence of GCH in our LPS rat model, which was related with augmented bronchiolar CD68 macrophage infiltration. The in-vitro experiments have shown that MUC5AC phenotype was inhibited when HBEC were challenged with supernatant from MDM pre-treated with or without LPS. In contrast, TNF-a and interleukin-1b at levels equivalent to supernatant from LPS-treated MDM increased MUC5AC. MUC5B was induced by LPS, supernatant from LPS-treated MDM, a mix of cytokines including TNF-a and TNF-a alone at levels present in supernatant from LPS-treated MDM. We demonstrated that macrophages are related with bronchiolar GCH, and that they induced MUC5B and inhibited MUC5AC in HBEC, suggesting a role for them in the pathogenesis of airway MUC5B-related GCH. KEYWORDS: airways; cytokines; LPS; lung inflammation; TNF-alphaMucus is a gel that covers the airway epithelium and is constituted by different glycoproteins called mucins, which are secreted by goblet cells from submucosal glands and the airway epithelium. 1 Mucus dissolves noxious gases and entraps foreign particles and pathogens, facilitating their clearance by mucociliary transport as a mechanism of innate defense. 2 However, in chronic inflammatory respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), there is a pathological goblet cell hyperplasia (GCH) and mucus hypersecretion that can generate airway occlusion, associated with morbidity and death. 1 The main gel-forming mucins found in human airways are MUC5B and MUC5AC. 1 In healthy individuals, low levels of MUC5B and MUC5AC can be detected in mucus; although MUC5B is mainly present in the submucosal glands and MUC5AC is predominantly distributed in the airway epithelium. 3 In baseline conditions of chronic inflammatory respiratory disorders, MUC5B and/or MUC5AC are increased in different compartments of the respiratory tract. [3][4][5][6] For example, MUC5B and MUC5AC are augmented in small airway lumen and epithelium from patients with advanced CF; 4 GC...

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Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Abstract: Bhattacharyya S, Dudeja PK, Tobacman JK. Lipopolysaccharide activates NF-B by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells.

Cited by 35 publications

References 31 publications

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-κB activation following carrageenan

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

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