Disease relevance of IL17F

• Association analysis of the interleukin 17 genes IL17A and IL17F as potential osteoarthritis susceptibility loci [1].
• Because IL-17A and IL-17F both regulate lung neutrophil recruitment, we measured these molecules as well as the proximal regulator IL-23p19 in the sputum of patients with cystic fibrosis (CF) undergoing pulmonary exacerbation [2].
• This proinflammatory activity is exemplified by their involvement in pulmonary inflammatory responses, in which both IL-17A and IL-17F are involved in the recruitment of neutrophils, and IL-17E is able to induce T H 2 cytokine production and eosinophilia [3].
• These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation [4].
• Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia, and mucin gene expression [4].

High impact information on IL17F

• RORgammat induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naïve CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17 [5].
• IL-17A and IL-17F production by T lymphocytes is regulated by IL-23 independent of T cell receptor activation [6].
• IL-17A and IL-17F both mobilize neutrophils partly through granulopoeisis and CXC chemokine induction, as well as increased survival locally [6].
• To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F [7].
• IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding [8].

Chemical compound and disease context of IL17F

• We studied the cellular uptake and retention of daunorubicin (D1) in two human leukemic cell lines (ML1 and K562) and myecloblasts from an untreated patient with acute myelogenous leukemia (AML) [9].

Biological context of IL17F

• A novel cytokine, ML-1, was recently discovered, which shares a similar sequence homology with, but is functionally distinct from, IL-17 (Kawaguchi, M., Onuchic, L., Li, X. D., Essayan, D. M., Schroeder, J., Xiao, H. Q., Liu, M. C., Krishnaswamy, G., Germino, G., and Huang, S. K. (2001) J. Immunol. 167, 4430-4435) [10].
• ML-1 gene expression was up-regulated in activated PBMCs, CD4(+) T cells, allergen-specific Th0, Th1, and Th2 clones, activated basophils, and mast cells [11].
• The polymorphisms identified in this study may be used in future studies of association between IL17F and phenotypes related to immune responses [12].
• None of the SNPs or haplotypes tested in IL17F were associated with asthma [12].
• We were thus interested in testing for association between single-nucleotide polymorphisms (SNPs) and haplotypes in IL17F and asthma [12].

Anatomical context of IL17F

• Results show that ML-1 induces in a time-dependent fashion the expression of IL-6 and IL-8 in both primary bronchial epithelial cells (PBECs) and human umbilical vein endothelial cells (HUVECs) [10].
• A novel gene, designated ML-1, was identified from a human genomic DNA clone and human T cell cDNA sequences [11].
• IL-17F was expressed only in activated CD4(+) T cells and activated monocytes [13].
• Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production [13].
• Recombinant human IL-17F did not stimulate the proliferation of hematopoietic progenitors or the migration of mature leukocytes [13].

Associations of IL17F with chemical compounds

• In this article, Margarita Dubocovich discusses the properties of melatonin receptors, and the basis for their classification into at least two subtypes, the ML1 and ML2 [14].
• A similar effect on ML1 cells was observed with the combination of bufalin with VP16 or human rTNF-alpha [15].
• Bufalin, under these conditions, induced the differentiation of U937, ML1, and HL60 cells to monocyte/macrophage-like cells by measuring the expression of various differentiation markers, as assessed by morphology and histochemistry, and ability to phagocytose latex particles, to reduce nitroblue tetrazolium, and to develop Fc receptors [15].
• CD protein expression was increased by exposure of ML1 cells to etoposide, adriamycin or gamma-radiation [16].
• Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose [17].

Regulatory relationships of IL17F

• mda-7 (IL-24) Inhibits growth and enhances radiosensitivity of glioma cells in vitro via JNK signaling [18].
• Together, these data indicates a role for Raf1-MEK-extracellular signal-regulated kinase 1/2 pathway in ML-1 induced C-X-C chemokine expression, suggesting potential pharmacological targets for modulation [19].
• Furthermore, overexpression of Raf1 dominant-negative mutants inhibited IL-17F-induced GMCSF expression [20].

Other interactions of IL17F

• These findings suggest that ML-1-induced IL-6 and IL-8 production is mediated through the activation of ERK1/2 in both cell types [10].
• Strikingly, treatment with IL-17A or IL-17F markedly reduced FRET efficiency, suggesting that IL-17RA subunits within the IL-17R complex undergo a conformational change upon ligand binding [21].
• Furthermore, increased expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence intensity (MFI) = 31.42 +/- 4.39 vs baseline, MFI = 12.26 +/- 1.77, p < 0.05), a functional feature distinct from IL-17 (MFI = 11.07 +/- 1.22) [11].
• In this report, we investigated the functional effect of ML-1 in the expression of growth-related oncogene (GRO)alpha and epithelial cell-derived neutrophil activating protein (ENA)-78 [19].
• Twelve amino acid substitutions in the two genes (IL17F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members [22].

Analytical, diagnostic and therapeutic context of IL17F

• A novel secreted cytokine, termed IL-17F, was cloned using nested RACE PCR [13].
• IL17F is expressed in lung tissue, in bronchoalveolar lavage fluid from asthmatic subjects, and in activated CD4+ cells [12].
• Additionally, recent clinical trials confirm safety and document significant clinical activity of mda-7/IL-24 in patients with diverse solid cancers and melanomas [23].
• U937 and ML1 cells started to differentiate at 4 and 6 h, respectively, after treatment with 10 nM bufalin and showed maximum differentiation 72 h later [15].
• The antitumor effect of ZD55-Gene (for example IL-24 gene) is much better than ZD55 (virotherapy) alone and hundred fold high than that of Ad-IL-24 (gene therapy) alone [24].

References