All-trans-Retinoic Acid Prevents Radiation- or Bleomycin-induced Pulmonary Fibrosis

Abstract

These data may provide a rationale to explore clinical use of ATRA for the prevention of radiation-induced lung fibrosis and other pathologic conditions involving pulmonary fibrosis.

Th2-like immune response in radiation-induced lung fibrosis

“…Buttner et al (9) and Huaux et al (10) reported elevated levels of the type 2 cytokine interleukin (IL)-4 in rats during RILF. Tabata et al (11) showed that all-trans-retinoic acid prevents RILF by suppressing the expression of IL-6 in mice lung tissue after irradiation. IL-10 was also found to be released in RILF (12).…”

Vitamin Levels in Lung Tissue of Rats with Bleomycin Induced Pulmonary Fibrosis

“…Tabata et al ( 32 ) checked the preventive effect of All-trans -RA (ATRA) on the progression of the fibrosis of lung in irradiated and BLM-treated rats. They found that ATRA will improve the fibrosis induced by BLM in the lung tissues of rats and their data may provide a reasoning to explore the clinical use of ATRA for the prevention of fibrosis induced by pathologic radiation of the lung implying pulmonary fibrosis.…”

All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice

“…ATRA (Sigma) was added to the growth medium to yield the final dimethyl sulfoxide (DMSO) solvent concentration ,0.05% (v/v). In some experiments, the cells were pre-incubated with proteasome inhibitor MG-132 (5 mM) [14], Jun N-terminal kinase (JNK) inhibitor SP600125 (10 mM) [15], p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (10 mM) [16] or extracellular signalregulated kinase (ERK)1/2 inhibitor PD98059 (25 mM) [13] for 60 min (all Calbiochem, San Diego, CA, USA). Animals 6-week-old C.B-17/Icr-scid Jcl (scid/scid) (SCID) female mice were purchased from Clea Japan (Tokyo, Japan) and maintained in our specific pathogen-free animal facility.…”

“…Injections were repeated three times weekly, 1) throughout the course, or 2) in the latter half of the period from inoculation to the end of the observation period. In previous studies, 0.5 mg of ATRA administration three times per week for 6 months did not produce noticeable morbidity and mortality [12,13]. The tumours were measured every 7 days with calipers, and their volumes were calculated using the formula a(b 2 )/2, in which a and b represent the longest and shortest diameters, respectively.…”

“…In a previous report, it was demonstrated that ATRA reduced irradiation-induced proliferation of lung fibroblasts by inhibiting both IL-6 production and IL-6R expression [12]. Moreover, it was recently reported that ATRA prevented both irradiationand bleomycin-induced pulmonary fibrosis in mice via an inhibitory effect on both IL-6-dependent fibroblast proliferation and transforming growth factor (TGF)-b1-dependent transdifferentiation of fibroblasts into myofibroblasts [13].…”