Disease relevance of IL17RD

• This putative receptor, which we have termed human SEF (hSEF), is also expressed in a variety of breast cancer tissues [1].
• These results suggest evidence that hSef is downregulated in advanced prostate cancer and might facilitate an enhanced tumorigenic response to FGFs [2].
• In contrast, metastasis was evident in only 10% (1/10) of tumours, which co-expressed both FGF8 and hSef (P<0.001) [2].
• Epidemiologic and animal challenge studies have suggested that SEF may play a critical role in toxic-shock syndrome [1] [3].
• Consequently, direct stimulation of PMN-derived, O2- mediated damage to endothelial cells is not a tenable hypothesis to explain the mechanism of SEF toxicity [3].

High impact information on IL17RD

• The position of the SEF 3 binding sequence corresponds with a previously reported seed-specific enhancer region, and it seems likely that this factor may act as a positive regulator of transcription of the beta-conglycinin, alpha' subunit gene in developing soybean seeds [4].
• One factor, SEF 3, binds exclusively to a region composed of two elements located at -183 to -169 base pairs and -153 to -134 base pairs relative to the start of transcription [4].
• Our results demonstrated that stably expressed hSef strongly inhibits FGF2- or nerve growth factor-induced PC-12 cell differentiation [5].
• Based on sequence and functional similarities, this novel IL-17 receptor homologue represents a potential human SEF and is likely to play critical roles in endothelial or epithelial functions such as proliferation, migration, and angiogenesis [1].
• hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling [5].

Chemical compound and disease context of IL17RD

• The binding of human fibronectin and Congo red by an autoaggregative Salmonella enteritidis strain was found to be dependent on its ability to produce thin, aggregative fimbriae, named SEF 17 (for Salmonella enteritidis fimbriae with an apparent fimbrin molecular mass of 17 kDa) [6].

Biological context of IL17RD

• Downregulation of endogenous hSef by hSef siRNA enhances the stimulus-induced ERK nuclear translocation and the activity of Elk-1 [7].
• Forced downregulation of hSef by siRNA increased FGF8b induced cell migration (P=0.02) and invasion (P=0.007) [2].
• CONCLUSIONS: IL-17RL exists as multiple isoforms due to extensive alternative splicing [8].
• A statistically significant correlation between the SEF ratio and the mean parotid dose was shown, with some recovery of function at 1 year after RT, comparable with the flow results [9].
• METHODS: A cDNA library of IL-17RL transcripts was arrayed onto nylon membranes [8].

Anatomical context of IL17RD

• A novel interleukin-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling [1].
• In a panel of cell lines, hSef was detected in both androgen-dependent and independent cells but was significantly reduced in highly metastatic derivative clones. hSef expression was not influenced by androgenic stimulation [2].
• We found that the tyrosine 330 is in the form of the YXXcapital EF, Cyrillic signal context and mutation of this residue resulted in preferred plasma membrane localization of hSef [10].
• This study did not address the possibility that SEF might indirectly activate PMN oxidative metabolism by promoting leukocytic pyrogen production by monocytes and macrophages [3] [3].
• The reduction in post-RT SEF correlated significantly with the mean parotid gland dose [9].

Associations of IL17RD with chemical compounds

• Tyrosine 330 in hSef is critical for the localization and the inhibitory effect on FGF signaling [10].
• Finally, SEF had no effect on O2- release by PMNs stimulated by PMA [3].
• PMN viability, as assessed by trypan blue exclusion, was unaffected by SEF [3].
• During propofol anesthesia, MEF increased at the low propofol infusion rate, but SEF was unaffected [11].
• Electrical stimulation in the reticular formation increased the spectral edge (SEF) and median edge (MEF) frequencies by approximately 1-2 Hz during halothane anesthesia at low and high concentrations [11].

Regulatory relationships of IL17RD

• Reduced hSef levels also enhanced FGF8b stimulated expression of MMP9 (P=0.005). mRNA in situ hybridization revealed hSef expression in 80% (8/10) of benign biopsies but in only 69% (23/33) of Gleason sum 4-7 and 35% (10/28) of Gleason sum 8-10 cancer biopsies (P=0.004) [2].

Other interactions of IL17RD

• The intracellular domain of hSef is necessary for the inhibitory effect on FGF2-induced PC-12 cell differentiation [5].
• These results thus demonstrate that hSef acts as a spatial regulator for ERK signaling by targeting ERK to the cytoplasm [7].
• The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE [12].

Analytical, diagnostic and therapeutic context of IL17RD

• Quantitative PCR of microdissected glands confirmed this trend (P=0.001). hSef was expressed in 69% (27/39) of non-metastatic tumours but in only 18% (2/11) of metastatic tumours (P=0.004, n=50). hSef expression was next correlated with earlier data on FGF8b expression in a subgroup of cancers [2].
• Immunoelectron microscopy of native fimbriae and Western blot (immunoblot) analysis of the corresponding 18-kDa fimbrins showed that these E. coli fimbriae were serologically cross-reactive with SEF 17 (Salmonella enteritidis fimbriae with a fimbrin molecular mass of 17 kDa) [13].
• Presumptive positive and representative negative strains were examined by Western blotting (immunoblotting) by using antiserum to SEF 17, the native GVVPQ fimbria of S. enteritidis [14].
• Furthermore, only SEF 17 was able to inhibit fibronectin binding to S. enteritidis whole cells in a direct competition enzyme-linked immunosorbent assay [6].
• At the high propofol infusion rate, SEF and MEF decreased following electrical stimulation in the reticular formation [11].

References