Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Authors: Lauritano, Dorina; Martinelli, Marcella; Baj, Alessandro; Beltramini, Giada; Candotto, Valentina; Ruggiero, Francesco; Palmieri, Annalisa
Abstract
Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast's function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 (CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts.
Enhanced proapoptotic gene expression of XAF1, CASP8 and TNFSF10 in the bovine endometrium during early pregnancy is not correlated with augmented apoptosis
PLACENTA
Authors: Groebner, A. E.; Schulke, K.; Unterseer, S.; Reichenbach, H. D.; Reichenbach, M.; Buettner, M.; Wolf, E.; Meyer, H. H. D.; Ulbrich, S. E.
Abstract
Bovine trophoblast cells release interferon-tau (IFNT), a type I IFN, as the pregnancy recognition signal. Since type I IFNs exert growth inhibitory and proapoptotic actions, the effect of the conceptus on components of the apoptosis pathways was determined in the bovine endometrium during the peri-mplantation period Uteri of Simmental heifers were flushed post mortem at days 12,15, and 18 of cycle or pregnancy for the recovery of conceptuses and the sampling of ipsilateral endometrial tissue at slaughter for quantitative RT-PCR, immunohistochemistry, caspase activity and TUNEL assays. Endometrium samples of pregnant animals revealed increased transcript levels for the proapoptotic genes XAF1 (day 15. 2 9-fold, day 18 15.1-fold; p = 0.005) and CASP8 (day 18 2.4-foid. p = 0.007) The mRNA expression increased significantly with the day of the cycle for the proapoptotic genes FASLG, TNFSF10, TNF and TNFSF1A (p = 0.004, p = 0,006, p = 0.001 and p = 0.007) and the antiapoptotic gene BIRC4 (p = 0 03) We detected high amounts of FASLG transcripts in day 18 conceptuses (16-fold higher than day 18 endometria) This finding was validated at the protein level by immunohistochemistry. To further analyse the endometrial activation of the caspase cascade, the activities of initiator caspase 8 and effector caspases 3/7 were determined Iuminometrically. No difference between pregnant and cyclic animals was found for either caspase activity Additionally, a TUNEL assay showed no increase of apoptotic cells in the pregnant endometrium In conclusion, although the bovine conceptus induces the expression of proapoptotic genes, neither an activation of a caspase cascade nor an increase of apoptotic cells was noticed These results suggest inhibitory mechanisms preventing endometrial cells from programmed cell death (C) 2009 Elsevier Ltd. All rights reserved.