Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of β-defensin-2 by staphylococcal peptidoglycan

Hussain, Tajamul; Nasreen, Najmunnisa; Lai, Yimu; Bellew, Brendan F.; Antony, Veena B.; Mohammed, Kamal A.

doi:10.1152/ajplung.00276.2007

Cited by 34 publications

(31 citation statements)

References 74 publications

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“…b-Defensins comprise a major subclass of the defensins (49) and play an important role in both innate and adaptive immune defense (50,51). They are chiefly expressed in a variety of epithelial cells (e.g., airway epithelia, urogenital tissues, nasolacrimal duct, and mammary gland) and sometimes immune cells (e.g., dendritic cells and macrophages) (50,52,53). Both humans and mice express a relatively large number of b-defensins, of which six human (hBD1-6) and five mouse (mBD1-5) defensins have been isolated and characterized.…”

Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

138

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Intestinal permeability plays a critical role in the etiopathogenesis of ulcerative colitis. Defensins, including porcine β-defensin (pBD)2, are crucial antimicrobial peptides for gut protection owing to their antibacterial and immunomodulatory activities. The purpose of this study was to investigate the protective effects of pBD2 on mucosal injury and the disruption of the epithelial barrier during the pathological process of dextran sodium sulfate (DSS)–induced colitis. The effects and mechanism of pBD2 were evaluated both using a DSS-induced C57BL/6 mouse model and, in vitro, using Caco-2 and RAW264.7 cells. DSS-induced colitis was characterized by higher disease activity index, shortened colon length, elevated activities of myeloperoxidase and eosinophil peroxidase, histologic evidence of inflammation, and increased expression levels of TNF-α, IL-6, and IL-8. pBD2 increased the expression of zonula occludens-1, zonula occludens-2, claudin-1, mucin-1, and mucin-2 mRNA and proteins, and it decreased permeability to FITC-D, as well as apoptosis, in DSS-treated mice. pBD2 also decreased inflammatory infiltrates of the colon epithelium. In Caco-2 cells, pBD2 increased transepithelial electrical resistance and mucin mRNA expression, and it decreased the permeability of FITC-D while preserving the structural integrity of the tight junctions. The effects of pBD2 appeared to be through upregulation of the expression of genes associated with tight junctions and mucins, and by suppressing DSS-induced increases in inflammation, inducible NO synthase, cyclooxygenase-2, and apoptosis. These results show that pBD2 improves DSS-induced changes in mucosal lesions and paracellular permeability, possibly by affecting the activation of NF-κB signaling. The present study demonstrates that intrarectal administration of pBD2 may be a novel preventive option for ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

138

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“…To our knowledge, PP is the first extracellular molecule reported to be a host factor in insect that regulates cellular immunity without direct opsonization of bacteria. Among the intracellular signaling pathways activated in infected hosts, p38 MAPK acts downstream of mammalian Toll-like receptors to produce AMPs (24). In mosquito Aedes aegypti, the p38 MAPK pathway is involved in AMP production induced by LPS (42).…”

Section: Discussionmentioning

confidence: 99%

Insect Cytokine Paralytic Peptide (PP) Induces Cellular and Humoral Immune Responses in the Silkworm Bombyx mori

Ishii

Hamamoto

Kamimura

et al. 2010

Journal of Biological Chemistry

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In the blood (hemolymph) of the silkworm Bombyx mori, the insect cytokine paralytic peptide (PP) is converted from an inactive precursor to an active form in response to the cell wall components of microorganisms and contributes to silkworm resistance to infection. To investigate the molecular mechanism underlying the up-regulation of host resistance induced by PP, we performed an oligonucleotide microarray analysis on RNA of blood cells (hemocytes) and fat body tissues of silkworm larvae injected with active PP. Expression levels of a large number of immune-related genes increased rapidly within 3 h after injecting active PP, including phagocytosis-related genes such as tetraspanin E, actin A1, and ced-6 in hemocytes, and antimicrobial peptide genes cecropin A and moricin in the fat body. Active PP promoted in vitro and in vivo phagocytosis of Staphyloccocus aureus by the hemocytes. Moreover, active PP induced in vivo phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in the fat body. Pretreatment of silkworm larvae with ML3403, a pharmacologic p38 MAPK inhibitor, suppressed the PP-dependent induction of cecropin A and moricin genes in the fat body. Injection of active PP delayed the killing of silkworm larvae by S. aureus, whereas its effect was abolished by preinjection of the p38 MAPK inhibitor, suggesting that p38 MAPK activation is required for PP-dependent defensive responses. These findings suggest that PP acts on multiple tissues in silkworm larvae and acutely activates cellular and humoral immune responses, leading to host protection against infection.

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“…Approximately 2 lg of RNA was reverse transcribed using the first-strand RT kit (Qiagen, SABiosciences). The transcript levels of interleukin (IL) 1; IL6; tumor necrosis factor (TNF) a; Kupffer cells (KC); regulated on activation, normal T cell expressed and secreted (RANTES); IL12; tolllike receptor (TLR) 2; and TLR9 was measured using primers described earlier (Hussain et al, 2008;Jayandharan et al, 2011) with a PCR master mix (MESA GREEN Mastermix plus, Eurogentec).…”

Section: Real-time Pcr Assaymentioning

confidence: 99%

Targeted Modifications in Adeno-Associated Virus Serotype 8 Capsid Improves Its Hepatic Gene Transfer Efficiency In Vivo

Sen

Gadkari

Sudha

et al. 2013

Human Gene Therapy Methods

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Recombinant adeno-associated virus vectors based on serotype 8 (AAV8) have shown significant promise for liver-directed gene therapy. However, to overcome the vector dose dependent immunotoxicity seen with AAV8 vectors, it is important to develop better AAV8 vectors that provide enhanced gene expression at significantly low vector doses. Since it is known that AAV vectors during intracellular trafficking are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal machinery, we modified specific serine/threonine kinase or ubiquitination targets on the AAV8 capsid to augment its transduction efficiency. Point mutations at specific serine (S)/threonine (T)/lysine (K) residues were introduced in the AAV8 capsid at the positions equivalent to that of the effective AAV2 mutants, generated successfully earlier. Extensive structure analysis was carried out subsequently to evaluate the structural equivalence between the two serotypes. scAAV8 vectors with the wild-type (WT) and each one of the S/T/Alanine (A) or K-Arginine (R) mutant capsids were evaluated for their liver transduction efficiency in C57BL/6 mice in vivo. Two of the AAV8-S/A mutants (S279A and S671A), and a K137R mutant vector, demonstrated significantly higher enhanced green fluorescent protein (EGFP) transcript levels (*9-to 46-fold) in the liver compared to animals that received WT-AAV8 vectors alone. The best performing AAV8 mutant (K137R) vector also had significantly reduced ubiquitination of the viral capsid, reduced activation of markers of innate immune response, and a concomitant two-fold reduction in the levels of neutralizing antibody formation in comparison to WT-AAV8 vectors. Vector biodistribution studies revealed that the K137R mutant had a significantly higher and preferential transduction of the liver (106 vs. 7.7 vector copies/mouse diploid genome) when compared to WT-AAV8 vectors. To further study the utility of the K137R-AAV8 mutant in therapeutic gene transfer, we delivered human coagulation factor IX (h.FIX) under the control of liver-specific promoters (LP1 or hAAT) into C57BL/6 mice. The circulating levels of h.FIX:Ag were higher in all the K137R-AAV8 treated groups up to 8 weeks post-hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel AAV8 vectors for potential gene therapy of hemophilia B.Introduction R ecombinant adeno-associated virus (AAV) vectors have gained significant attention as a gene therapy vector due to their lack of pathogenicity and their ability to infect different tissues (Flotte and Carter, 1995;Choi et al., 2005;Wu et al., 2006;Mueller and Flotte, 2008). So far, 12 serotypes of AAV (AAV1 to AAV12) vectors have been studied extensively as gene therapy vectors (Schultz and Chamberlain, 2008). These AAV serotypes share a common genome, but their unique capsid structure helps them recognize different cell-surface receptors (Grimm and Kay, 2003). AAV serotype 2 is the most extensively studied but has demonstrated only limited precli...

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Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of β-defensin-2 by staphylococcal peptidoglycan

Cited by 34 publications

References 74 publications

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Insect Cytokine Paralytic Peptide (PP) Induces Cellular and Humoral Immune Responses in the Silkworm Bombyx mori

Targeted Modifications in Adeno-Associated Virus Serotype 8 Capsid Improves Its Hepatic Gene Transfer Efficiency In Vivo

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