Department of Internal Medicine III, University of Giessen, Germany.
Innate Immun. 2021 Feb;27(2):184-191. doi: 10.1177/1753425920988167. Epub 2021 Jan 28.
Recent data argue for a pro-inflammatory role of CAMP (cathelicidin antimicrobial peptide) in adipocytes and adipose tissue (AT) and for regulatory circuits involving TLRs. In order to investigate regulatory effects of TLR2 and TLR4, 3T3-L1 adipocytes were stimulated with TLR2 agonistic lipopeptide MALP-2 and with TLR4 agonist LPS in presence or absence of signal transduction inhibitors. CAMP gene expression was analysed by quantitative real-time PCR in adipocytes and in murine AT compartments and cellular subfractions. CAMP expression was higher in gonadal than in subcutaneous AT and there was a gender-specific effect with higher levels in males. Adipocytes had higher CAMP expression than the stroma-vascular cell (SVC) fraction. MALP-2 up-regulated CAMP expression significantly, mediated by STAT3 and PI3K and potentially (non-significant trend) by NF-κB and MAPK, but not by raf-activated MEK-1/-2. Moreover, LPS proved to act as a potent inducer of CAMP via NF-κB, PI3K and STAT3, whereas specific inhibition of MAPK and MEK-1/-2 had no effect. In conclusion, activation of TLR2 and TLR4 by classical ligands up-regulates adipocyte CAMP expression involving classical signal transduction elements. These might represent future drug targets for pharmacological modulation of CAMP expression in adipocytes, especially in the context of metabolic and infectious diseases.
最近的数据表明，CAMP（抗菌肽）在脂肪细胞和脂肪组织（AT）中具有促炎作用，并且涉及 TLR 的调节回路。为了研究 TLR2 和 TLR4 的调节作用，用 TLR2 激动性脂肽 MALP-2 和 TLR4 激动剂 LPS 刺激 3T3-L1 脂肪细胞，存在或不存在信号转导抑制剂。通过定量实时 PCR 在脂肪细胞和鼠脂肪组织隔室和细胞亚群中分析 CAMP 基因表达。在性腺 AT 中 CAMP 的表达高于皮下 AT，并且存在性别特异性效应，男性水平更高。脂肪细胞的 CAMP 表达高于基质血管细胞（SVC）部分。MALP-2 通过 STAT3 和 PI3K 显著上调 CAMP 表达，并且可能通过 NF-κB 和 MAPK（非显著趋势）上调，但不受 raf 激活的 MEK-1/-2 影响。此外，LPS 被证明通过 NF-κB、PI3K 和 STAT3 作为 CAMP 的有效诱导剂，而 MAPK 和 MEK-1/-2 的特异性抑制没有作用。总之，经典配体激活 TLR2 和 TLR4 上调脂肪细胞 CAMP 表达，涉及经典信号转导元件。这些可能成为脂肪细胞中 CAMP 表达的药理学调节的未来药物靶点，特别是在代谢和感染性疾病的背景下。
