LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells

Smirnova, Marina G.; Guo, Li; Birchall, John P.; Pearson, Jeffrey P.

doi:10.1016/s0008-8749(03)00059-5

Cited by 176 publications

(123 citation statements)

References 33 publications

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“…52 Of note, LPS was able to consistently induce mainly MUC5B in HBEC, similar to the effect reported in the goblet cell line HT29-MTX. 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.…”

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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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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“…This hypothesis has been investigated in a few studies. For example, it has been observed that the LPS of gram-native bacteria increases the expression of the mRNA of MUC5AC and MUC5B and stimulates the secretion of MUC5AC and MUC5B mucins (359). The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C 12 -HSL)] of gram-negative bacteria could stimulate the production of a major mucin core protein, MUC5AC (174).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Lactobacillus plantarum strain 299v increases the levels of expression of the mRNA of mucins MUC2 and MUC3, thus in turn inhibiting the cell attachment of EPEC, an effect that can be mimicked by adding purified exogenous MUC2 and MUC3 mucins (231,232). Moreover, it has been observed that LPS of gram-negative bacteria increases the expression of the mRNA of MUC5AC and MUC5B and stimulates the secretion of MUC5AC and MUC5B mucins (359). It has been recently demonstrated that the secreted mucins including MUC5AC together with membrane-bound mucins, contributes to host defense by preventing bacterial invasion of the intestinal cells.…”

Section: Barrier Effect Against Pathogensmentioning

confidence: 99%

The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota

2006

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SUMMARY The intestinal tract is a complex ecosystem that combines resident microbiota and the cells of various phenotypes with complex metabolic activities that line the epithelial wall. The intestinal cells that make up the epithelium provide physical and chemical barriers that protect the host against the unwanted intrusion of microorganisms that hijack the cellular molecules and signaling pathways of the host and become pathogenic. Some of the organisms making up the intestinal microbiota also have microbicidal effects that contribute to the barrier against enteric pathogens. This review describes the two cell lineages present in the intestinal epithelium: the goblet cells and the Paneth cells, both of which play a pivotal role in the first line of enteric defense by producing mucus and antimicrobial peptides, respectively. We also analyze recent insights into the intestinal microbiota and the mechanisms by which some resident species act as a barrier to enteric pathogens. Moreover, this review examines whether the cells producing mucins or antimicrobial peptides and the resident microbiota act in partnership and whether they function individually and/or synergistically to provide the host with an effective front line of defense against harmful enteric pathogens.

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“…However, CD14-deficient cells are also able to respond to LPS in the presence of serum (Hailman et al, 1994), and the intestinal epithelial cell lines HT29 and Caco-2 are sensitive (monitored via IL-8 expression) to pathogen-derived LPS in serum-containing media (Schuerer-Maly et al, 1994;Smirnova et al, 2003;Huang et al, 2003), thus suggesting the potential for epithelial sensitivity to commensal-derived LPS moieties. In addition, mutations of the TLR-4 gene have been implicated in the pathogenesis of inflammatory bowel disease (Franchimont et al, 2004;Oostenbrug et al, 2005), further demonstrating a possible role for commensalderived LPSs in intestinal homeostasis.…”

Section: Lipopolysaccharidementioning

confidence: 99%

Exploring the immunomodulatory potential of microbial-associated molecular patterns derived from the enteric bacterial microbiota

Patten

Collett

2013

Microbiology

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The human intestinal lumen represents one of the most densely populated microbial niches in the biological world and, as a result, the intestinal innate immune system exists in a constant state of stimulation. A key component in the innate defence system is the intestinal epithelial layer, which acts not only as a physical barrier, but also as an immune sensor. The expression of pattern recognition receptors, such as Toll-like receptors, in epithelial cells allows innate recognition of a wide range of highly conserved bacterial moieties, termed microbial-associated molecular patterns (MAMPs), from both pathogenic and non-pathogenic bacteria. To date, studies of epithelial immunity have largely concentrated on inflammatory pathogenic antigens; however, this review discusses the major types of MAMPs likely to be produced by the enteric bacterial microbiota and, using data from in vitro studies, animal model systems and clinical observations, speculates on their immunomodulatory potential. IntroductionThe intestine represents the body's largest mucosal surface, with the adult human intestine estimated to cover an area of about 250 m 2 (Artis, 2008). The highly folded luminal surface of the intestinal wall significantly increases absorption efficiency and, as such, is the largest surface area of the body exposed to the environment and its high microbial load (DeSesso & Jacobson, 2001). Humans have co-evolved with indigenous microbial populations, termed microbiota, which inhabit various niches of the body (Hooper et al., 2012) and the adult intestine is one of the most densely populated microbial habitations in the biological world (Artis, 2008). The enteric microbiota predominantly consists of bacteria, with estimated populations of~10 14 bacteria, with up to 500 species represented (Gill et al., 2006;Guarner & Malagelada, 2003); however, methanogenic archaea, eukaryotes (yeasts) and viruses (mainly bacteriophages) are also present (Lozupone et al., 2012). Due to the vast expanse of intestinal tissue exposed to the microbiota, the local innate immune system is in a constant state of stimulation, and a chronic, low-level proinflammatory response is characteristic of enteric immune homeostasis (Macpherson & Harris, 2004;Artis, 2008).The intestinal epithelium plays an active role in innate immunity, and pattern recognition receptors (PRRs) are utilized to detect the presence of bacteria and their associated antigens. PRRs are germline-encoded, sensory molecules which recognize a range of highly conserved bacterial motifs, termed 'pathogen-associated molecular patterns' (PAMPs) (Medzhitov, 2001). However, the ability of PRRs to recognize these bacterial moieties is not limited to just pathogens, and so the term 'microbial-associated molecular patterns' (MAMPs) may be more accurate (Medzhitov, 2001; Sanderson & Walker, 2007) and will be used throughout this review. Epithelium-associated, enteric immune cells, such as macrophages, dendritic cells, T-cells and B-cells, differentially express two major groups of PRRs, th...

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LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells

Cited by 176 publications

References 33 publications

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

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

The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota

Exploring the immunomodulatory potential of microbial-associated molecular patterns derived from the enteric bacterial microbiota

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