The Chromosomal Protein HMGN2 Mediates the LPS-Induced Expression of β-Defensins in Mice

Deng, Lijing; Wu, Guangxin; Cao, Yue; Fan, Bo; Gao, Xiang; Tang, Xiaohai; Huang, Ning

doi:10.1007/s10753-011-9335-3

Cited by 14 publications

(15 citation statements)

References 32 publications

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“…This is consistent with prior reports which observed increases in mBD3 and mBD4 expression in the tongue and stomach of Candida infected mice (39, 40). It was recently discovered that mBD3 and mBD4 upregulation requires the high mobility group nucleosomal binding domain 2 protein (HMGN2), a chromatin binding protein; however, mBD1 expression was shown to be independent of HMGN2, indicating that basal mBD1 expression may be uniquely regulated and a critical component of early mucosal responses (41). We observed a significant reduction in mBD2 and mBD4 expression in DEFB1 −/− mice when compared to WT, demonstrating a possible cross-regulation of these peptides.…”

Section: Discussionmentioning

confidence: 99%

β-Defensin 1 Plays a Role in Acute Mucosal Defense against Candida albicans

Tomalka

Azodi

Narra

et al. 2015

The Journal of Immunology

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Candida is an opportunistic fungal pathogen that colonizes the mucosal tract of humans. Pathogenic infection occurs in the presence of conditions causing perturbations to the commensal microbiota or host immunity. Early innate immune responses by the epithelium, including antimicrobial peptides (AMPs) and cytokines, are critical for protection against overgrowth. Reduced salivary AMP levels are associated with oral Candida infection and certain AMPs, including human beta-defensins 1 - 3, have direct fungicidal activity. Here we demonstrate that murine β-Defensin 1 (mBD1) is important for control of early mucosal Candida infection and plays a critical role in the induction of innate inflammatory mediators. Mice deficient in mBD1 exhibit elevated oral and systemic fungal burdens as compared to wild-type mice. Neutrophil infiltration to the sites of mucosal Candida invasion, an important step in limiting fungal infection, is significantly reduced in mBD1 deficient mice. These mice also exhibit defects in the expression of other antimicrobial peptides, including mBD2 and mBD4, which may have direct anti-Candida activity. We also show that mBD1 deficiency impacts the production of important anti-fungal inflammatory mediators including IL-1β, IL-6, KC, and IL-17. Collectively, these studies demonstrate a role for the mBD1 peptide in early control of Candida infection in a murine model of mucosal candidiasis, as well as on the modulation of host immunity through augmentation of leukocyte infiltration and inflammatory gene induction.

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Section: Discussionmentioning

confidence: 99%

β-Defensin 1 Plays a Role in Acute Mucosal Defense against Candida albicans

Tomalka

Azodi

Narra

et al. 2015

The Journal of Immunology

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“…Since 2004, we firstly identified HMGN2 functioned as an antimicrobial peptides, and furthermore, we have demonstrated that HMGN2 is a multifunctional protein in immune regulation. For example, we found that HMGN2 promotes LPS‐induced β‐defensin expression in lung epithelial cells . HMGN2 inhibits the internalization of Klebsiella pneumoniae in lung epithelial cell A549 through decreasing the expression and activity of α5β1 integrin and activated FAK‐Src signalling to reduce F‐actin polymerization .…”

Section: Introductionmentioning

confidence: 89%

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

Wang

Chen

Ren

et al. 2019

J Cellular Molecular Medi

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Non‐tuberculous mycobacteria (NTM), also known as an environmental and atypical mycobacteria, can cause the chronic pulmonary infectious diseases. Macrophages have been suggested as the main host cell to initiate the innate immune responses to NTM infection. However, the molecular mechanism to regulate the antimicrobial immune responses to NTM is still largely unknown. Current study showed that the NTM clinical groups, Mycobacterium abscessus and Mycobacterium smegmatis, significantly induced the M1 macrophage polarization with the characteristic production of nitric oxide (NO) and marker gene expression of iNOS, IFNγ, TNF‐α, IL1‐β and IL‐6. Interestingly, a non‐histone nuclear protein, HMGN2 (high‐mobility group N2), was found to be spontaneously induced during NTM‐activated M1 macrophage polarization. Functional studies revealed that HMGN2 deficiency in NTM‐infected macrophage promotes the expression of M1 markers and the production of NO via the enhanced activation of NF‐κB and MAPK signalling. Further studies exhibited that HMGN2 knock‐down also enhanced IFNγ‐induced M1 macrophage polarization. Finally, we observed that silencing HMGN2 affected the survival of NTM in macrophage, which might largely relevant to enhanced macrophage polarization into M1 phenotype under the NTM infection. Collectively, current studies thus suggested a novel function of HMGN2 in regulating the anti‐non‐tuberculous mycobacteria innate immunity of macrophage.

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“…HMGN2 expression is downregulated during the physiological processes of myogenesis, erythrogenesis and chondrogenesis, as well as during embryonic organ formation, such as kidney development (10). Abnormal expression of the HMGN2 gene or protein has been associated with the development of neoplasms and autoimmune diseases (25)(26)(27). However, due to the poorly defined biological functions of this protein, further research is required.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of high-mobility group nucleosomal-binding domain 2 protein in various tumor cell lines

Chen

et al. 2018

Oncol Lett

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Abstract. High mobility group nucleosomal-binding domain 2 (HMGN2) is an abundant non-histone nuclear protein of vertebrates and invertebrates. The aim of the present study was to characterize the endogenous expression of HMGN2 in various types of tumor cell. Western blotting was performed to analyze HMGN2 expression in the following tumor cell lines: H1975, HSC-4, MDA-MB-468, MDA-MB-231, SCC-25 and THP-1. Periodontal ligament cells (PDLCs) were included as a noncancerous control. HMGN2 was detected in human oral squamous cell carcinoma tissues by immunohistochemical analysis. The results demonstrated that the expression of HMGN2 was increased in the majority of tumor cell lines, particularly MDA-MB-468 and THP-1 cells, compared with PDLCs. The expression of HMGN2 in oral squamous cell carcinoma tissue was significantly increased compared with the expression in normal tissue. Furthermore, the expression of HMGN2 in metastatic oral squamous cell carcinoma tissues was increased compared with that in its non-metastatic counterpart. These results indicated that HMGN2 may serve an important function in the growth and metastasis of tumor cells.

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The Chromosomal Protein HMGN2 Mediates the LPS-Induced Expression of β-Defensins in Mice

Cited by 14 publications

References 32 publications

β-Defensin 1 Plays a Role in Acute Mucosal Defense against Candida albicans

β-Defensin 1 Plays a Role in Acute Mucosal Defense against Candida albicans

HMGN2 regulates non‐tuberculous mycobacteria survival via modulation of M1 macrophage polarization

Increased expression of high-mobility group nucleosomal-binding domain 2 protein in various tumor cell lines

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