To investigate the effect of signal transducers and activators of transcription 1(STAT1)antisense oligonucleotides(ASON)on concentrations of TNF-α,IL-8,NO secreted by alveolar macrophages(AMs)in bleomycin-induced ratpulmonary fibrosis,five adult female Wistar rats were intratracheally instilled with bleomycin.After 7 days,therats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia and bronehoalveolar lavage(BAL)was performed to obtain AMs.AMs were divided into four groups,treated with STAT1 ASON,STAT1 senseoligonucleotides(SON),dexamethasone(DEX)and medium alone(control),respectively.AMs and media werecollected after culture for 36h.The mRNA and protein expressions of STAT1 and ICAM-1 in AMs were detectedby RT-PCR and ELISA,respectively.The concentrations of TNF-α,IL-8,NO in cultured medium were detected.The STAT1 mRNA expression by AMs in the STAT1 ASON group was lower than those of AMs in the STAT1 SONgroup,the DEX group and the control group(p<0.05).Moreover,the STAT1 mRNA expression by AMs in theDEX group was also lower than those of AMs in the STAT1 SON group and the control group(p<0.05),but theSTAT1 mRNA expression by AMs in the STAT1 SON group was not different from that of the control group(p>0.05).The protein expressions of STAT1 and ICAM-1 and the mRNA expression of ICAM-1 showed similarchanges to the STAT1 mRNA expression by AMs.The concentrations of TNF-α,IL-8,NO in cultured medium fromSTAT1 ASON group were lower than those from STAT1 SON,DEX and the control groups(p<0.05).Moreover,the concentrations of TNF-α,IL-8,NO in cultured medium from DEX group were also lower than those from thecontrol and STAT1 SON group(p<0.05),but no difference between STAT1 SON group and the control(p>0.05).The results suggest that STAT1 ASON could inhibit the secretion of TNF-α,IL-8,NO in AMs,and STAT1 couldbecome a target of treating pulmonary fibrosis.Cellular & Molecular Immunology.2005;2(3):211-217. To investigate the effect of signal transducers and activators of transcription 1 (STAT1) antisense oligonucleotides on concentrations of TNF-α, IL-8, NO secreted by alveolar macrophages (AMs) in bleomycin-induced ratpulmonary fibrosis, five adult female Wistar rats were intratracheally instilled with bleomycin. After 7 days, therats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia and bronehoalveolar lavage (BAL) was performed to obtain AMs.AMs were divided into four groups, treated with STAT1 ASON, STAT1 senseoligonucleotides ( SON), dexamethasone (DEX) and medium alone (control), respectively.AMs and media were collected after culture for 36h.The mRNA and protein expressions of STAT1 and ICAM-1 in AMs were detected by RT-PCR and ELISA, respectively. of TNF-α, IL-8, NO in cultured medium were detected. STAT1 mRNA expression by AMs in the STAT1 ASON group was lower than those of AMs in the STAT1 SONgroup, the DEX group and the control group (p <0.05) . Moreover, the STAT1 mRNA expression by AMs in the STAT group was also lower than those of AMs in the STAT1 SON group and the control group (p <0.05), but the STAT1 mRNA expression by AMs in the STAT1 SON group was not different from that of the control group (p> 0.05). The protein expressions of STAT1 and ICAM-1 and the mRNA expression of ICAM-1 were similar to the STAT1 mRNA expression by AMs. The concentrations of TNF-α, IL-8, The concentrations of TNF-α, IL-8, NO in cultured medium from DEX group were also lower than those from the control and STAT1 SON group (p <0.05), but no difference between STAT1 SON group and the control (p> 0.05). The results suggest that STAT1 ASON could inhibit the secretion of TNF-α, IL-8, NO in AMs, and STAT1 could become a target of treating pulmonary fibrosis. Cellular & Molecular Immunology. 2005; 2 (3): 211-217.