Peptidoglycan

Peptidoglycan from Bacillus subtilis(Peptidoglycan) is a major component of the bacterial cell wall and is a polymer composed of sugars and amino acids. Peptidoglycan forms a mesh-like layer outside the bacterial cell membrane, providing structural strength and rigidity to the bacteria. Peptidoglycan also acts as a bioactive molecule to regulate the development, physiology, and pathology of eukaryotic cells ^[1]. Peptidoglycan is composed of long linear glycan chains cross-linked by short peptide stems. The glycan chains consist of repeating units of the disaccharide N-acetylglucosamine-β(1,4)-N-acetylmuramic acid[GlcNAc-β(1,4)-MurNAc], and the peptide stems are typically composed of alternating L-amino acids and D-amino acids ^[2]. Peptidoglycan is involved in modulating the activity of various signaling pathways and has the capacity to activate the immune response of the host, often being used as a disease inducer ^{[3, 4]}.

In vitro, Peptidoglycan(20μg/ml) stimulates Toll-like receptor 2(TLR2) on the surface of keratinocytes, promoting the expression of JNK/MAPK and FosB signaling pathways stimulated by the aryl hydrocarbon receptor to enhance the activity of the IL-1β and IL-6 promoters, ultimately stimulating an inflammatory response ^[5]. Peptidoglycan(200μg/ml) can promote the secretion of TNF-α and IL-6 by activated macrophages, while increasing the activity of the NF-κB and MAPK signaling pathways ^[6].

In vivo, Peptidoglycan(1.2mg/kg/day) was administered via intraperitoneal injection to male C57BL/6 mice for 4 weeks. Peptidoglycan did not alter food intake or body weight gain in mice but severely impaired glucose tolerance and insulin sensitivity. Peptidoglycan increased the fat mass and epididymal fat tissue weight of mice, as well as plasma and hepatic triglyceride levels and plasma cholesterol content ^[7]. Peptidoglycan(5mg/kg/day) was injected intravitreally into BALB/c mice for 6 hours. Peptidoglycan increased the number of inflammatory cells infiltrating the iris of the mice, including the number of rolling, adhering, and infiltrating leukocytes ^[8].

 References:
[1] Bastos PAD, Wheeler R, Boneca IG. Uptake, recognition and responses to peptidoglycan in the mammalian host. FEMS Microbiol Rev. 2021 Jan 8;45(1):fuaa044.
[2] Vollmer W, Blanot D, de Pedro MA. Peptidoglycan structure and architecture. FEMS Microbiol Rev. 2008 Mar;32(2):149-67.
[3] Kolonitsiou F, Syrokou A, Karamanos NK, et al. Immunoreactivity of 80-kDa peptidoglycan and teichoic acid-like substance of slime producing S. epidermidis and specificity of their antibodies studied by an enzyme immunoassay. J Pharm Biomed Anal. 2001 Jan;24(3):429-36.
[4] Caruso R, Warner N, Inohara N, et al. NOD1 and NOD2: signaling, host defense, and inflammatory disease. Immunity. 2014 Dec 18;41(6):898-908.
[5] Wang L, Cheng B, Ju Q, et al. AhR Regulates Peptidoglycan-Induced Inflammatory Gene Expression in Human Keratinocytes. J Innate Immun. 2022;14(2):124-134.
[6] Wang F, Li Y, Yang C, et al. Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses. Mediators Inflamm. 2019 Jan 9;2019:1349784.
[7] Jin M, Lai Y, Zhao P, et al. Effects of peptidoglycan on the development of steatohepatitis. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Apr;1865(4):158595.
[8] Rosenzweig HL, Galster K, Vance EE, et al. NOD2 deficiency results in increased susceptibility to peptidoglycan-induced uveitis in mice. Invest Ophthalmol Vis Sci. 2011 Jun 9;52(7):4106-12.

Peptidoglycan from Bacillus subtilis(Peptidoglycan)是细菌细胞壁的主要成分，由糖类和氨基酸组成的聚合物。Peptidoglycan在细菌细胞膜外形成网状层，为细菌提供结构强度和刚性。Peptidoglycan还作为生物活性分子以调节真核细胞的发育、生理和病理过程^[1]。Peptidoglycan由短肽茎交联的长线性聚糖链组成。聚糖链由二糖N-乙酰葡糖胺-β（1,4）-N-乙酰胞壁酸[GlcNAc-β（1,4）-MurNAC]的重复单元组成，肽茎通常由交替的L-氨基酸和D-氨基酸组成^[2]。Peptidoglycan参与调节多种信号通路的活性，可激活机体免疫反应的能力，常被用于疾病的诱导剂^{[3, 4]}。

在体外，Peptidoglycan（20μg/ml）刺激角质形成细胞表面的toll样受体2(TLR2)，促进芳烃受体刺激的 JNK/MAPK 和 Fosb信号通路的表达以增强IL-1β和IL-6的启动子的活性，最终刺激炎症反应^[5]。Peptidoglycan（200μg/ml）可促进活化的巨噬细胞分泌TNF-α和 IL-6，同时增加NF-κB和MAPK信号通路的活性^[6]。

在体内，Peptidoglycan（1.2mg/kg/day）通过腹腔注射至雄性C57BL6小鼠4周，Peptidoglycan不会改变小鼠的食物摄入量和体重增长，但是对小鼠的葡萄糖耐量和胰岛素敏感性造成了严重的损害；Peptidoglycan增加了小鼠的脂肪量和附睾脂肪组织重量，同时提高血浆和肝脏甘油三酯水平，以及血浆胆固醇含量^[7]。Peptidoglycan（5mg/kg/day）通过玻璃体内注射至BALB/c小鼠6小时，Peptidoglycan增加了小鼠虹膜内的炎性细胞浸润，包括滚动、粘附和浸润的白细胞数量^[8]。