title: Azithromycin acts as an immunomodulatory agent to suppress the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis.
abstract: Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed in inflammatory lesions caused by infectious agents such as bacteria and fungi but not in normal tissues or non-infectious lesions. There is evidence that macrolide antibiotics can act as immunomodulatory agents. The purpose of the current study was to determine whether azithromycin, a type of macrolide antibiotic, could reduce the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis in vitro and in vivo. We treated THP-1 cells with LPS, LPS+TREM-1/Fc, and LPS+azithromycin for in vitro study. A B. pyocyaneus pyemia animal model was developed for in vivo study. RT-PCR, western blotting, and flow cytometry (FCM) were employed to determine the expression of TREM-1. ELISA analysis was utilized to examine the concentration of cytokines. Our results showed that azithromycin treatment did not reduce the level of LPS-induced TREM-1 mRNA in THP-1 cells. However, treatment with TREM-1/Fc fusion protein or azithromycin reduced the effect of LPS-stimulated TREM-1 protein expression. The expression of inflammatory factors (TNF-α, IL-6, and IL-1β) in cell culture supernatant and mouse serum of the TREM-1/Fc fusion protein-treated and azithromycin-treated groups were lower than that of the control group (p<0.05). The results from the animal sepsis model experiments demonstrated that the TREM-1 Fc/fusion protein and azithromycin treatment groups' survival rates were significantly higher than in the control group. Analysis of serum inflammatory factors in septic mice revealed that the concentration of these factors was significantly lower than in the control group. Our results furthered the understanding of azithromycin function in immunological regulation and provided reliable data for new clinical applications.
authors.affiliation: Institute of Respiratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tong
authors.forename: Zeng-Chang
authors.initials: ZC
authors.lastname: Liu
authors.forename: Dao-Xin
authors.initials: DX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000494:pharmacology*; D001407:Bacillus / Q000254:growth & development; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D018796:Immunoconjugates / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D015996:Survival Rate; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D018796:Immunoconjugates; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin