Abstract
Extensive studies focused on the therapeutic efficacy of epigallocatechin-3-gallate (EGCG) against bacterial infection. However, little is known about its prophylactic efficacy against bacterial infection. Herein, we found that EGCG showed an effective prophylactic efficacy against bacterial infection with a broad spectrum, including Gram-negative, Gram-positive, and drug-resistant bacteria. Pretreatment with EGCG through intraperitoneal injection, intravenous injection, or intragastric administration significantly reduced the bacterial load, inflammatory response, and mortality in mouse abdominal infection models induced by bacterial inoculation or cecal ligation and puncture. Pretreatment with EGCG by intraperitoneal injection significantly increased the numbers of neutrophils and monocytes/macrophages in the abdominal cavity and peripheral blood of mice, and depletion of neutrophils and monocytes/macrophages by specific antibodies or chemical drugs obviously increased the bacterial load in mice. Of note, EGCG did not directly induce neutrophil and macrophage migration, and it just induced phagocyte migration in the presence of macrophages in a co-cultured system, implying that EGCG-induced phagocyte migration relies on its immunoregulatory effects on macrophages. EGCG markedly induced the production of cytokines and chemokines in macrophages and mouse peritoneal lavage, including tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), IL-6, CXC chemokine ligands 1 and 2 (CXCL1 and 2), and monocyte chemotactic protein-1 (MCP-1). EGCG significantly induced the phosphorylation of p38 and JNK mitogen-activated protein kinases (MAPKs) in macrophages, and inhibition of p38 and JNK MAPKs markedly reduced EGCG-induced chemokine and cytokine production. Anti-67-kDa laminin receptor (67LR) antibody treatment significantly reduced EGCG-induced chemokine production and p38 and JNK phosphorylation in macrophages. Together, EGCG showed an obvious prophylactic efficacy against bacterial infection by inducing a pro-inflammatory response in macrophages through the 67LR/p38/JNK signaling pathway, supporting the further development of EGCG as a potent prophylaxis for bacterial infection and providing new clues to understand the healthcare function of green tea.
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