An increased resistance to surgical site infections has been associated with surgical meshes composed of naturally occurring materials, including poly-4-hydroxybutrate (4HB). 4HB is a naturally occurring short-chain fatty acid that has been shown to promote endogenous expression of the Cramp gene coding for the antimicrobial peptide (AMP) cathelicidin LL-37 in murine bone marrow-derived macrophages. The molecular pathways involved in the 4HB-induced cathelicidin LL-37 expression have not yet been identified. The present study showed that transcriptional activation of the Cramp gene by 4HB is independent of inhibition of histone deacetylase (HDAC) activity, and that upregulation of Cramp is modulated by the G-protein coupled receptor GPR109A. Furthermore, an intracellular signaling cascade that promotes the activation of the MAP kinases, p38 and JNK, and a subsequent NF-κB phosphorylation downstream from p38 is essential for the AMP transcriptional response in 4HB-stimulated macrophages. The findings provide a solid scientific basis and rationale for the decreased incidence of surgical site infections with the use of this type of surgical meshes. Further clinical significance is found in the fact that the 4HB activated molecular pathway includes common targets of frequently used nonsteroidal anti-inflammatory drugs (NSAIDs) and other FDA approved drugs recognizing G-protein coupled receptors.

对由天然存在的材料（包括聚4-羟基丁酸酯（4HB））组成的手术网片，增加了对手术部位感染的抵抗力。4HB是天然存在的短链脂肪酸，已显示在鼠骨髓源性巨噬细胞中可促进编码抗菌肽（AMP）cathelicidin LL-37的Cramp基因的内源表达。尚未确定参与4HB诱导的cathelicidin LL-37表达的分子途径。本研究表明4HB对Cramp基因的转录激活独立于对组蛋白脱乙酰基酶（HDAC）活性的抑制，以及Cramp的上调由G蛋白偶联受体GPR109A调节。此外，细胞内信号传导级联可促进MAP激酶，p38和JNK的活化，以及随后p38下游的NF-κB磷酸化，对于4HB刺激的巨噬细胞中的AMP转录反应至关重要。这些发现为使用这种类型的手术网减少手术部位感染的发生率提供了坚实的科学基础和理由。在以下事实中发现了进一步的临床意义：4HB激活的分子途径包括常用的非甾体抗炎药（NSAID）和其他FDA认可的识别G蛋白偶联受体的药物的共同靶点。