Dehydroandrographolide enhances innate immunity of intestinal tract through up-regulation the expression of hBD-2

Xiong, Wenbi; Shao, Zhen-Jun; Xiong, Yao; Chen, Jian; Sun, Yun; Zhu, Ling; Zhou, Liming

doi:10.1186/s40199-015-0119-4

Cited by 15 publications

(16 citation statements)

References 35 publications

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“…TLR2 signaling induces the activation of multiple downstream pathways such as MAPK and NF-κB (Karikó et al, 2004), both of which are known to increase hBD2 expression (Ogushi et al, 2001; Vora et al, 2004; Wehkamp et al, 2004; Li et al, 2008; Xiong et al, 2015). Our results show that hBD2 level was suppressed by pretreatment with the JNK inhibitor SP600125 in LH2171 SLP-treated cells; in addition, treatment with LH2171 SLP activated JNK signaling in Caco-2 cells whereas TLR2 blockade reduced JNK signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Cellular components of LAB are recognized by pattern recognition receptors such as TLR expressed by host cells, which activate intracellular signaling pathways (Shida et al, 2009; Kawashima et al, 2013; Kim et al, 2015; Kobatake et al, 2017). Many studies have investigated the regulation of hBD2 expression with variable findings (Ogushi et al, 2001; Vora et al, 2004; Wehkamp et al, 2004; Li et al, 2008; Xiong et al, 2015), underscoring the difficulty in establishing the beneficial effects and mechanisms of action of LAB. Our observation that Lactobacillus SLP induces a host defense response could contribute to the elucidation of LAB functions.…”

Section: Discussionmentioning

confidence: 99%

“…Human (h)BD1, hBD2, and hBD3 have been extensively studied; hBD2 and hBD3 are induced by inflammation or bacteria (Harder et al, 2001; Ganz, 2003), whereas hBD1 is constitutively expressed. For example, vitamin D (De Filippis et al, 2017), ceramide-1-phosphate (Kim et al, 2014), various plant secondary metabolites (Schwab et al, 2008; Lombardo Bedran et al, 2014; Xiong et al, 2015), and bacterial factors (Ogushi et al, 2001) are known to induce BD expression in epithelial cells. Thus, increasing BD expression is expected to prevent infections.…”

Section: Introductionmentioning

confidence: 99%

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S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human β-Defensin 2 Expression via TLR2–JNK Signaling

Kobatake

Kabuki

2019

Front. Microbiol.

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Antimicrobial peptides that contribute to innate immunity are among the most important protective measures against infection in many organisms. Several substances are known to regulate the expression of antimicrobial peptides. In this study, we investigated the factors in lactic acid bacteria (LAB) that induce antimicrobial peptide expression in the host. We found that Lactobacillus helveticus SBT2171 (LH2171) induced the expression of human β-defensin (hBD)2 in Caco-2 human colonic epithelial cells. Specifically, surface layer protein (SLP) of LH2171 stimulated hBD2 expression by activating c-Jun N-terminal kinase (JNK) signaling via Toll-like receptor (TLR)2 in Caco-2 cells. SLPs extracted from other lactobacilli similarly increased hBD2 expression, suggesting that this stimulatory effect is common feature of Lactobacillus SLPs. Interestingly, Lactobacillus strains that strongly induced hBD2 expression also potently activated JNK signaling. Thus, upregulation of hBD2 induced by TLR2–JNK signaling contributes to protection of the host against infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human β-Defensin 2 Expression via TLR2–JNK Signaling

Kobatake

Kabuki

2019

Front. Microbiol.

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“…Although we have preliminarily described the anti-inflammatory effect of Deh and its effect on intestinal flora in vivo , the mechanism of its anti-inflammatory effect in vivo is still unclear. Wenbi Xiong et al found that Deh upregulates hBD-2 to enhance the innate immunity of the intestine [ 20 ]. Our study found that Deh significantly activated the AMPK signaling pathway and promoted the phosphorylation of AMPK.…”

Section: Discussionmentioning

confidence: 99%

Dehydroandrographolide inhibits mastitis by activating autophagy without affecting intestinal flora

Guo

Liu

Zhang

et al. 2020

Aging

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Mastitis can seriously damage the physical and mental health of lactating women. The use of antibiotics and anti-inflammatory drugs may damage the flora balance in lactating women. To alleviate mastitis in lactating women and reduce drug-induced damage to the flora, we found that dehydroandrographolide (Deh) has good anti-inflammatory and bacterial balance functions. In vivo , we found that Deh significantly inhibited the expression of MPO, IL6, IL-1β, TNF-α, COX2 and iNOS and reduced pathological damage to the mammary gland. The feces in the control and Deh groups were collected and sequenced for 16S flora. The results showed that Deh did not change the primary intestinal microflora composition of the two groups. In vitro , our study showed that Deh significantly inhibited the expression of IL6, IL-1β and TNF-α in the EpH4-Ev cell line. When an AMPK inhibitor was added, the anti-inflammatory effect of Deh was blocked. To further study the anti-inflammatory mechanism of Deh, we found that Deh significantly promoted autophagy through the phosphorylation of AMPK, Beclin and ULK1. In conclusion, our study found that Deh promoted autophagy and played an anti-inflammatory role by activating the AMPK/Beclin/ULK1 signaling pathway and did not affect intestinal flora.

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“…Human β-defensin-2 (HBD2) is an inducible antimicrobial peptide [ 19 ]. In addition, it exhibits cytolytic activity against a range of tumor cells that is thought either to destabilize the cellular membrane or to cause the formation of open pores which allow vital biomolecules leaking out of the cell.…”

Section: Introductionmentioning

confidence: 99%

A recombinantly tailored β-defensin that displays intensive macropinocytosis-mediated uptake exerting potent efficacy against K-Ras mutant pancreatic cancer

Shang

Sheng

et al. 2016

Oncotarget

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K-Ras mutant pancreatic cancer cells display intensive macropinocytosis, indicating that this process may be exploited in the design of anticancer targeted therapies. In this study, we constructed a macropinocytosis-oriented recombinantly tailored defensin (DF-HSA) which consists of human β-defensin-2 (DF) and human serum albumin (HSA). The macropinocytosis intensity and cytotoxicity of DF-HSA were investigated in K-Ras mutant MIA PaCa-2 cells and wild-type BxPC-3 cells. As found, the DF-HSA uptake in MIA PaCa-2 cells was much higher than that in wild-type BxPC-3 cells. Correspondingly, the cytotoxicity of DF-HSA to MIA PaCa-2 cells was more potent than that to BxPC-3 cells. In addition, the cytotoxicity of DF-HSA was much stronger than that of β-defensin HBD2. DF-HSA suppressed cancer cell proliferation and induced mitochondrial pathway apoptosis. Notably, DF-HSA significantly inhibited the growth of human pancreatic carcinoma MIA PaCa-2 xenograft in athymic mice at well tolerated dose. By in vivo imaging, DF-HSA displayed a prominent accumulation in the tumor. The study indicates that the recombinantly tailored β-defensin can intensively enter into the K-Ras mutant pancreatic cancer cells through macropinocytosis-mediated process and exert potent therapeutic efficacy against the pancreatic carcinoma xenograft. The novel format of β-defensin may play an active role in macropinocytosis-mediated targeting therapy.

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Dehydroandrographolide enhances innate immunity of intestinal tract through up-regulation the expression of hBD-2

Cited by 15 publications

References 35 publications

S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human β-Defensin 2 Expression via TLR2–JNK Signaling

S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human β-Defensin 2 Expression via TLR2–JNK Signaling

Dehydroandrographolide inhibits mastitis by activating autophagy without affecting intestinal flora

A recombinantly tailored β-defensin that displays intensive macropinocytosis-mediated uptake exerting potent efficacy against K-Ras mutant pancreatic cancer

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