Löntz W, Sirsjö A, Liu W, Lindberg M, Rollman O, Törmä H
Department of Dermatology, University Hospital, Uppsala, Sweden.
Free Radic Biol Med. 1995 Feb;18(2):349-55. doi: 10.1016/0891-5849(94)e0124-2.
Because reactive oxygen species have been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of the antioxidant enzyme superoxide dismutase was studied in psoriatic skin tissue. By using reverse transcription-PCR we found similar expression of copper, zinc superoxide dismutase (CuZnSOD) in the involved vs. uninvolved psoriatic skin. In contrast, the level of the manganese superoxide dismutase (MnSOD) mRNA message was consistently higher in lesional psoriatic skin as compared to adjacent uninvolved skin and healthy control skin. Parallel investigation of those cytokines that are thought to be direct or indirect inducers of the MnSOD activity revealed an increased mRNA expression of IL-1 beta, TNF-alpha, and GM-CSF in lesional psoriatic skin. To study if these cytokines exert a direct effect on dismutase expression in epidermal cells, human keratinocytes in culture were challenged with IL-1 beta, TNF-alpha, and GM-CSF. It was found that IL-1 beta and TNF-alpha, but not GM-CSF, induced the mRNA expression of MnSOD, and an additive effect was demonstrated for the two former cytokines. Further, the expression of both CuZnSOD and MnSOD transcripts was similar in cultured keratinocytes maintained at low differentiation (low Ca2+ medium) and cells forced to terminal differentiation (by high Ca2+ medium). Our results indicate that the abnormal expression of MnSOD mRNA in lesional psoriatic skin is not directly linked to the pathologic state of keratinocyte differentiation in the skin. It seems more likely that the cutaneous overexpression of MnSOD in psoriatic epidermis represents a protective cellular response evoked by cytokines released from inflammatory cells invading the diseased skin.
由于活性氧与多种过度增殖性和炎性疾病的发病机制有关，因此研究了抗氧化酶超氧化物歧化酶在银屑病皮肤组织中的mRNA表达。通过逆转录聚合酶链反应，我们发现在银屑病受累皮肤与未受累皮肤中铜锌超氧化物歧化酶（CuZnSOD）的表达相似。相比之下，与相邻的未受累皮肤和健康对照皮肤相比，银屑病皮损皮肤中锰超氧化物歧化酶（MnSOD）mRNA水平始终较高。对那些被认为是MnSOD活性直接或间接诱导剂的细胞因子进行的平行研究显示，银屑病皮损皮肤中IL-1β、TNF-α和GM-CSF的mRNA表达增加。为了研究这些细胞因子是否对表皮细胞中的歧化酶表达有直接影响，用IL-1β、TNF-α和GM-CSF刺激培养的人角质形成细胞。结果发现，IL-1β和TNF-α可诱导MnSOD的mRNA表达，而GM-CSF则不能，并且前两种细胞因子具有相加作用。此外，在低分化（低钙培养基）培养的角质形成细胞和被迫终末分化（高钙培养基）的细胞中，CuZnSOD和MnSOD转录本的表达相似。我们的结果表明，银屑病皮损皮肤中MnSOD mRNA的异常表达与皮肤角质形成细胞分化的病理状态没有直接联系。银屑病表皮中MnSOD的皮肤过度表达似乎更可能是由侵入患病皮肤的炎性细胞释放的细胞因子引起的一种保护性细胞反应。
