il-40

2-heptyl-3-hydroxy-4(1H)-Quinolone (Pseudomonas Quinolone Signal) 是一种铜绿假单胞菌为应对细胞密度增加而产生的一种法定人数感应信号分子。 它增加了铜绿假单胞菌中lasB 基因的表达，增加代谢物焦蓝蛋白和凝集素PA-IL 的分泌，以及增加铜绿假单胞菌种群的生物膜生产。当使用浓度为40 μM 时，它还会降低铜绿假单胞菌生长介质中的铁含量，并在硫酸铁溶液中充当一种铁螯合剂。

STING agonist 12b is an agonist of stimulator of interferon genes (STING).1It binds to STING (Kd= 26.4 μM) and induces interferon reporter gene expression in cells expressing human or mouse STING (EC50s = 7.45 and 10.23 μM, respectively). STING agonist 12b (40 μM) induces expression of TNF-a, IL-6, IP-10, and IL-1b in THP-1 cells. 1.Hou, S., Lan, X.-j., Li, W., et al.Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonistsBioorg. Chem.95103556(2020)

AC708 is a small molecule CSF1R inhibitor that effectively inhibits CSF1R phosphorylation mediated by CSF-1 (IC50 = 26 nM) and IL-34 (IC50 = 33 nM). It also inhibited the activity of growth factor-dependent cells cultured in CSF-1 (IC50 = 38 nM) or IL-34

Cathelicidin-2 (CATH-2) (128-153) 是一种合成抗菌肽，对应于鸡CATH-2的128至153个氨基酸。该化合物对E. coli、S. aureus、S. enteritidis和B. globigii展示出浓度依赖性的活性。CATH-2 (128-153) (40 µM) 可诱导孤立的鸡红细胞溶解，但对孤立的人外周血单个核细胞(PBMCs)无细胞毒性。它能促进化学因子(C-C-基序)配体2 (CCL2)的产生，并抑制LPS诱导的TNF-α、IL-6、IL-8和IL-10在孤立的人PBMCs中的产生。

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

β-Defensin-2 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius.2β-Defensin-2 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes.3It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-2 induces IL-31 production by human peripheral blood-derived mast cellsin vitrowhen used at a concentration of 10 μg/ml and by rat mast cellsin vivofollowing a 500 ng intradermal dose.4Expression of β-defensin-2 is increased in psoriatic skin and chronic wounds.5,6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 3.Niyonsaba, F., Ushio, H., Nakano, N., et al.Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokinesJ. Invest. Dermatol.127(3)594-604(2007) 4.Niyonsaba, F., Ushio, H., Hara, M., et al.Antimicrobial peptides human β-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cellsJ. Immunol.184(7)3526-3534(2010) 5.Huh, W.-K., Oono, T., Shirafuji, Y., et al.Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skinJ. Mol. Med. (Berl.)80(10)678-684(2002) 6.Butmarc, J., Yufit, T., Carson, P., et al.Human β-defensin-2 expression is increased in chronic woundsWound Repair Regen.12(4)439-443(2004)

DGKζ-IN-6 (compound 40) 作为一种口服活性DGKζ抑制剂，显示出45.5 nM的IC50值。它能够抑制IL-2的分泌，适用于癌症及自身免疫疾病的相关研究。

Compound (R)-7, 一种抗炎剂,在LPS处理的RAW细胞中显示出显著的效果,将亚硝酸盐和IL-6的水平分别降低了32%和40%.

Avenanthramide-C methyl ester is an inhibitor of NF-κB activation that acts by blocking the phosphorylation of IKK and IκB (IC50 ~ 40 μM). Through this mechanism, avenanthramide-C methyl ester dose dependently inhibits the expression and secretion of IL-6, IL-8, and MCP-1 in human aortic endothelial cells.

1,1'-Ethylidene-bis-(L-tryptophan) is a potential impurity in L-tryptophan commercial products, promoting EoL-3 eosinophilic leukemia cell proliferation, enhancing eosinophil cationic protein release from human peripheral blood eosinophils, and boosting IL-5 production in human T cells. At 40 µg kg, it triggers fascia thickening, mast cell infiltration, inflammation, and fibrosis in mouse superficial adipose and panniculus carnosus tissues, serving as an eosinophilia-myalgia syndrome research model.

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.