Department of Experimental Medicine, Microbiology and Clinical Microbiology Section, Second University of Naples, Italy.
Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1167-76. doi: 10.1177/039463201002300420.
Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.
唇疱疹是单纯疱疹病毒 1 型（HSV-1）感染最常见的临床特征。上皮细胞能够对 HSV-1 的存在作出反应，诱导白细胞介素 6（IL-6）、白细胞介素 1（IL-1）、肿瘤坏死因子-α（TNF-α）和白细胞介素 8（IL-8）的表达。这些前炎性细胞因子在急性期反应的调节、趋化作用、炎性细胞的激活和抗原呈递细胞中发挥作用。在人类上皮细胞模型中，已经证明，在宿主的早期前炎性反应诱导之后，HSV-1 通过两种病毒蛋白 ICP4 和 ICP27 的积累来下调前炎性细胞因子的产生，这两种病毒蛋白的转录由被称为衣壳蛋白 VP16 的被膜蛋白诱导。这些病毒蛋白通过减少前炎性基因的 mRNA 的稳定性，延迟细胞因子的产生，从而使病毒得以复制。此外，病毒反式激活蛋白 ICP-0 和 VP-16 诱导白细胞介素 10（IL-10）的表达。唇疱疹的传统治疗方法包括局部和全身使用抗病毒药物，但需要找到新的治疗方法，这些方法可以在病毒感染中以选择性和非细胞毒性的方式发挥作用。激光二极管治疗已被认为是传统治疗唇疱疹疼痛、炎症调节和伤口愈合的替代方法。本研究旨在报告激光二极管照射在预防和减少唇疱疹病毒唇疱疹病变严重程度方面的可能作用机制。我们在 HaCat 上皮细胞的体外模型中研究了激光对 HSV-1 复制的影响，并评估了某些前炎性细胞因子（TNF-α、IL-1β 和 IL-6）、抗菌肽 HBD2、趋化因子 IL-8 和免疫抑制细胞因子 IL-10 的表达调节。我们的结果使我们假设 LD 照射作用于 HSV-1 复制的最后阶段，通过限制病毒从一个细胞到另一个细胞的传播，并且激光治疗也作用于宿主的免疫反应，解除了在上皮细胞感染中由子代病毒积累引起的前炎性介质抑制。
