IL26 gene inactivation in Equidae
ANIMAL GENETICS
Authors: Shakhsi-Niaei, M.; Droegemueller, M.; Jagannathan, V.; Gerber, V.; Leeb, T.
Abstract
Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution.
Cultured human periodontal ligament cells constitutively express multiple osteotropic cytokines and growth factors, several of which are responsive to mechanical deformation
JOURNAL OF PERIODONTAL RESEARCH
Authors: Pinkerton, Mark N.; Wescott, David C.; Gaffey, Benjamin J.; Beggs, Kyle T.; Milne, Trudy J.; Meikle, Murray C.
Abstract
Background and Objective: A role for cytokines and growth factors in mediating the cellular and molecular events involved in orthodontic tooth movement is well established. The focus to date, however, has been largely on individual mediators, rather than to study cytokines in terms of complex interacting networks. Our objective was to expand our knowledge of the cytokines and growth factors expressed by human periodontal ligament (PDL) cells and to identify new genes that are responsive to mechanical deformation. Material and Methods: Human PDL cells were strained with a cyclic deformation of 12% for 6-24 h, and the differential expression of 79 cytokine and growth factor genes was quantified using real-time RT-PCR arrays. For statistical comparison, t-tests were used with mean critical threshold (CT) values derived from triplicate samples. Results: Forty-one genes were detected at CT values < 35 and, of these, 15 showed a significant change in relative expression. These included seven interleukins (IL): IL1A, IL1F7, IL6 and IL7 (down), IL8, IL11 and IL12A (up). Eight genes representing other cytokine and growth factor families showed comparable mechanical sensitivity, including VEGFD and OPG (down) and PDGFA, INHBA, GDF8 and two transforming growth factor beta genes, TGFB1 and TGFB3 (up). The genes CSF2/GMCSF and IL11 were found to be consistently stimulated across all three time points. Genes that were not expressed included: (1) the immunoregulatory lymphokines (IL2-IL5), IL17 and IL17B; (2) IL10 and other members of the IL-10 family of anti-inflammatory cytokines (IL19, IL20, IL22 and IL24); and (3) TNF and RANKL. Conclusion: Human PDL cells constitutively express numerous osteotropic cytokines and growth factors, many of which are mechanoresponsive.