1. Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects
K M Haapasaari, J Risteli, A Oikarinen Br J Dermatol. 1996 Jul;135(1):65-9.
In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21-26 years (mean 23), and old subjects, aged 55-70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin, indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.
2. Radiation-induced changes in skin type I and III collagen synthesis during and after conventionally fractionated radiotherapy
Riitta Keskikuru, Arja Jukkola, Jouni Nuutinen, Vesa Kataja, Juha Risteli, Pekka Autio, Tapani Lahtinen Radiother Oncol. 2004 Mar;70(3):243-8. doi: 10.1016/j.radonc.2003.11.014.
Background and purpose: To measure local changes of collagen metabolism in irradiated breast skin and systemic changes in serum during and after radiotherapy and correlate these changes with skin thickness, erythema and palpable subcutaneous induration. Patients and methods: Aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively) were measured from skin suction blister fluid (SBF) in 21 breast cancer patients with breast conserving surgery and conventionally fractionated radiotherapy (RT) to a total dose of 50Gy. Suction blisters were induced in the operated and contralateral breast skin before RT, at 2.5 weeks, at the end of RT, and at 1, 4, 7, 12 and 24 months post-treatment. Blood samples for serum were taken simultaneously with SBF induction. Skin thickness of the suction blister sites was measured with a high-frequency ultrasound device. The investigated sites were scored for erythema at the end of RT and palpable subcutaneous induration at 1 and 2 years post-treatment. Results: In SBF the mean levels of PINP and PIIINP of the operated breast before RT were about 3-4 times higher than those in the contralateral breast due to the operation-related wound healing. The synthesis of PINP in irradiated breast after RT increased 7.7-fold (P < 0.001) 4 months post-irradiation. The PIIINP synthesis was at maximum at 1 month post-irradiation (P < 0.001). Both synthesis stayed elevated until 2 years. The level of PINP correlated significantly with the palpable skin induration at 1 and 2 years (P = 0.038 and P = 0.003, respectively). The skin thickness of the irradiated breast was highest at 4 months post-treatment and significantly elevated until 1 year. The skin thickness correlated with the PINP level until 7 months and with PIIINP between 4 and 18 months. The PINP/PIIINP ratio reached the maximum at 4 months and stayed elevated until 2 years. No change in mean serum level of PINP was found during or after RT. Conclusions: We demonstrated a maximum and elevated levels for PINP and PIIINP skin collagen metabolism determined from SBF during the 2 years' follow-up. Elevated levels of PINP and PIIINP correlated with the thickening of the skin and subcutaneous induration but not with erythema.
3. The production of collagen and the activity of mast-cell chymase increase in human skin after irradiation therapy
Riitta Riekki, Ilkka T Harvima, Arja Jukkola, Juha Risteli, Aarne Oikarinen Exp Dermatol. 2004 Jun;13(6):364-71. doi: 10.1111/j.0906-6705.2004.00164.x.
Fibrosis is a common complication of radiotherapy. The pathogenesis of radiation-induced fibrosis is not known in detail. There is increasing evidence to suggest that mast cells contribute to various fibrotic conditions. Several mast-cell mediators have been proposed to have a role in fibrogenesis. Tryptase and chymase, the predominant proteins in mast cells, have been shown to induce fibroblast proliferation and collagen synthesis in vitro. In order to explore the role of mast cells in irradiation-induced fibrosis, we analyzed skin biopsies and suction blister fluid (SBF) samples from the lesional and healthy-looking skin of 10 patients who had been treated for breast cancer with surgery and radiotherapy. The biopsies were analyzed histochemically for mast-cell tryptase, chymase, kit receptor, and tumor necrosis factor-alpha. Skin collagen synthesis was assessed by determining the levels of type I and III procollagen amino-terminal propeptides (PINP and PIIINP) in SBF and using immunohistochemical staining for PINP. Immunohistochemical stainings for prolyl-4-hydroxylase reflecting collagen synthesis and chymase immunoreactivity in irradiated and control skin were also performed. The mean level of procollagen propeptides in SBF, which reflects actual skin collagen synthesis in vivo, was markedly increased in irradiated skin compared to corresponding healthy control skin areas. The mean number of PINP-positive fibroblasts was also significantly increased in the upper dermis of radiotherapy-treated skin. The number of cells positive for tryptase, chymase and kit receptor was markedly increased in irradiated skin. In addition, using double-staining techniques, it was possible to demonstrate that in some areas of the dermis, tryptase-positive mast cells and fibroblasts are closely associated. These findings suggest a possible role of mast cells in enhanced skin collagen synthesis and fibrosis induced by radiotherapy.
