Información del artículo
Abstract
The lip vermillion constitutes a transition tissue, between oral mucosa and skin, where oral mucosal cells from epithelial and connective tissue compartments are exposed to ultraviolet (UV) sunlight. Fibroblasts are abundant resident cells of the connective tissue which are key regulators of extracellular matrix composition, as well as, epithelial and endothelial cell function. UVB light, an inherent component of sunlight, causes several alterations in skin fibroblasts, including premature senescence and increased cyclooxygenase COX-2 expression. To assess if UVB irradiation had similar effects on fibroblasts derived from human oral mucosa (HOM), primary cultures of HOM fibroblasts were irradiated with a single dose of 30 or 60mJ/cm2 of UVB light or sham-irradiated. Fibroblast proliferation was assessed from 3 to 48hrs after UVB-irradiation utilizing [3H]-thymidine incorporation and MTT assays. In addition, COX-2 mRNA expression was detected by RT-PCR, and PGE2 production was assessed using enzyme immunoassay from 0.5 to 24hrs after UVB-irradiation. The results showed a significant decrease in proliferation of UVB-irradiated HOM fibroblasts as compared to controls as measured by both [3H]-thymidine incorporation and MTT assays (p<0.001). HOM fibroblasts had increased COX-2 mRNA expression at 0.5 and 12hrs after irradiation, and PGE2 production was elevated at 12 and 24hrs post-irradiation as compared to controls (p<0.05). The results showed an inhibitory effect of a single dose of UVB irradiation on HOM fibroblast proliferation with an increase in COX-2 expression and activation. Therefore, photodamaged fibroblasts may play and important role in the pathogenesis of UV-induced lesions of the lip.
Key words:
Oral fibroblasts
UVB
COX-2
proliferation
PGE2
El Texto completo está disponible en PDF
Referencias bibliográficas
[1.]
R.C. Lundeen, R.P. Langlais, G.T. Terezhalmy.
Sunscreen protection for lip mucosa: a review and update.
J Am Dent Assoc, 111 (1985), pp. 617-621
[2.]
G.E. Kaugars, T. Pillion, J.A. Svirsky, D.G. Page, J.C. Burns, L.M. Abbey.
Actinic cheilitis: a review of 152 cases.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 88 (1999), pp. 181-186
[3.]
J.E. Rundhaug, S.M. Fischer.
Cyclo-oxygenase-2 plays a critical role in UV-induced skin carcinogenesis.
Photochem Photobiol, 84 (2008), pp. 322-329
[4.]
M. Yaar, B.A. Gilchrest.
Photoageing: mechanism, prevention and therapy.
Br J Dermatol, 157 (2007), pp. 874-887
[5.]
I.G. Rojas, A. Martínez, U. Brethauer, et al.
Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR- 2.
Oral Oncol, 45 (2009), pp. 284-290
[6.]
A. Martínez, U. Brethauer, J. Borlando, M.L. Spencer, I.G. Rojas.
Epithelial expression of p53, mdm-2 and p21 in normal lip and actinic cheilitis.
Oral Oncol, 44 (2008), pp. 878-883
[7.]
D.R. Neto Pimentel, N. Michalany, M. Alchorne, M. Abreu, R.C. Borra, L. Weckx.
Actinic cheilitis: histopathology and p53.
J Cutan Pathol, 33 (2006), pp. 539-544
[8.]
C. Rosette, M. Karin.
Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors.
Science, 274 (1996), pp. 1194-1197
[9.]
G.J. Clydesdale, G.W. Dandie, H.K. Muller.
Ultraviolet light induced injury: immunological and inflammatory effects.
Immunol Cell Biol, 79 (2001), pp. 547-568
[10.]
S. Yokoo, S. Yamagami, T. Mimura, et al.
UV absorption in human oral mucosal epithelial sheets for ocular surface reconstruction.
Ophthalmic Res, 38 (2006), pp. 350-354
[11.]
S.T. McKeown, J.J. Barnes, P.L. Hyland, F.T. Lundy, M.J. Fray, C.R. Irwin.
Matrix metalloproteinase-3 differences in oral and skin fibroblasts.
J Dent Res, 86 (2007), pp. 457-462
[12.]
P. Stephens, K.J. Davies, N. Occleston, et al.
Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity.
Br J Dermatol, 144 (2001), pp. 229-237
[13.]
W. Chen, J. Kang, J. Xia, et al.
p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts.
Int J Mol Med, 21 (2008), pp. 645-653
[14.]
F. Debacq-Chainiaux, C. Borlon, T. Pascal, et al.
Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway.
J Cell Sci, 118 (2005), pp. 743-758
[15.]
V. Marwaha, Y.H. Chen, E. Helms, et al.
T-oligo treatment decreases constitutive and UVB-induced COX-2 levels through p53- and NFkappaBdependent repression of the COX-2 promoter.
J Biol Chem, 280 (2005), pp. 32379-32388
[16.]
K.L. Tober, T.A. Wilgus, D.F. Kusewitt, J.M. Thomas-Ahner, T. Maruyama, T.M. Oberyszyn.
Importance of the EP(1) receptor in cutaneous UVB-induced inflammation and tumor development.
J Invest Dermatol, 126 (2006), pp. 205-211
[17.]
T.M. Oberyszyn.
Non-melanoma skin cancer: importance of gender, immunosuppressive status and vitamin D.
Cancer Lett, 261 (2008), pp. 127-136
[18.]
J.K. Williams, S.F. Davidson, S.G. Johnson, H.S. Hsu, S.K. Das.
An in vitro study on the effect of UVA radiation on human gingival fibroblasts.
Br J Plast Surg, 45 (1992), pp. 349-353
[19.]
W. Lim, M. Ko, S. Lee, et al.
Ultraviolet-C-induced apoptosis protected by 635-nm laser irradiation in human gingival fibroblasts.
Photomed Laser Surg, 26 (2008), pp. 215-220
[20.]
Y.C. Chang, C.H. Tsai, S.H. Yang, C.M. Liu, M.Y. Chou.
Induction of cyclooxygenase-2 mRNA and protein expression in human gingival fibroblasts stimulated with nicotine.
J Periodontal Res, 38 (2003), pp. 496-501
[21.]
S. Nakao, Y. Ogata, H. Sugiya.
Nicotine stimulates the expression of cyclooxygenase-2 mRNA via NFkappaB activation in human gingival fibroblasts.
Arch Oral Biol, 54 (2009), pp. 251-257
[22.]
C.H. Tsai, M.Y. Chou, Y.C. Chang.
The up-regulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis.
J Oral Pathol Med, 32 (2003), pp. 146-153
[23.]
T. Yucel-Lindberg, H. Ahola, S. Nilsson, J. Carlstedt-Duke, T. Modéer.
Interleukin-1 beta induces expression of cyclooxygenase-2 mRNA in human gingival fibroblasts.
Inflammation, 19 (1995), pp. 549-560
[24.]
H. Larvaja, J. Heino, V. Kahari, T. Krusius, E. Vuorio.
Characterization of one phenotype of human periodontal granulation-tissue fibroblasts.
J Dent Res, 68 (1989), pp. 20-25
[25.]
D.W. Gilroy, M.A. Saunders, L. Sansores-Garcia, N. Matijevic-Aleksic, K.K. Wu.
Cell cycle-dependent expression of cyclooxygenase-2 in human fibroblasts.
FASEB J, 15 (2001), pp. 288-290
[26.]
T.A. Wilgus, A.T. Koki, B.S. Zweifel, P.A. Rubal, T.M. Oberyszyn.
Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B-induced skin cancer.
Mol Carcinog, 38 (2003), pp. 33-39
[27.]
M.I. Rudolph, Y. Boza, R. Yefi, et al.
The influence of mast cell mediators on migration of SW756 cervical carcinoma cells.
J Pharmacol Sci, 106 (2008), pp. 208-218
[28.]
G. Chan, J.O. Boyle, E.K. Yang, et al.
Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck.
Cancer Res, 59 (1999), pp. 991-994
[29.]
D. Baram, G.G. Vaday, P. Salamon, I. Drucker, R. Hershkoviz, Y.A. Mekori.
Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha.
J Immunol, 167 (2001), pp. 4008-4016
[30.]
E. Straface, R. Vona, B. Ascione, et al.
Single exposure of human fibroblasts (WI-38) to a sub-cytotoxic dose of UVB induces premature senescence.
FEBS Lett, 581 (2007), pp. 4342-4348
[31.]
F. Chainiaux, J.P. Magalhaes, F. Eliaers, J. Remacle, O. Toussaint.
UVB-induced premature senescence of human diploid skin fibroblasts.
Int J Biochem Cell Biol, 34 (2002), pp. 1331-1339
[32.]
M.S. Choi, M.S. Yoo, D.J. Son, et al.
Increase of collagen synthesis by obovatol through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast.
J Dermatol Sci, 46 (2007), pp. 127-137
[33.]
T. Mosmann.
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
J Immunol Methods, 65 (1983), pp. 55-63
[34.]
K.K. Wu.
Differential cyclooxygenase-2 transcriptional control in proliferating versus quiescent fibroblasts.
Prostaglandins Other Lipid Mediat, 83 (2007), pp. 175-181
[35.]
R. Kalluri, M. Zeisberg.
Fibroblasts in cancer.
Nat Rev Cancer, 6 (2006), pp. 392-401
[36.]
M.P. Charalambous, T. Lightfoot, V. Speirs, K. Horgan, N.J. Gooderham.
Expression of COX-2, NF-kappaB-p65 NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue.
Br J Cancer, 101 (2009), pp. 106-115
[37.]
K. Kourelis, G. Vandoros, T. Kourelis, T. Papadas, P. Goumas, G. Sotiropoulou-Bonikou.
Low COX-2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression.
Laryngoscope, 119 (2009), pp. 1723-1729
[38.]
T. Matsuzuka, K. Miller, L. Pickel, C. Doi, R. Ayuzawa, M. Tamura.
The synergistic induction of cyclooxygenase-2 in lung fibroblasts by angiotensin II and pro-inflammatory cytokines.
Mol Cell Biochem, 320 (2009), pp. 163-171
[39.]
T.A. Wilgus, A.T. Koki, B.S. Zweifel, D.F. Kusewitt, P.A. Rubal, T.M. Oberyszyn.
Inhibition of cutaneous ultraviolet light B-mediated inflammation and tumor formation with topical celecoxib treatment.
Mol Carcinog, 38 (2003), pp. 49-58
[40.]
M. Vukadinovic, Z. Jezdic, M. Petrovic, L.M. Medenica, M. Lens.
Surgical management of squamous cell carcinoma of the lip: analysis of a 10-year experience in 223 patients.
J Oral Maxillofac Surg, 65 (2007), pp. 675-679
Copyright © 2010. Sociedad de Periodoncia de Chile, Sociedad de Implantología Oral de Chile y Sociedad de Prótesis y Rehabilitación Oral de Chile