Regulation of transforming growth factor Il1 (TGFII1), TGF(2, and TGF0i3 mRNAs in murine fibroblasts and keratinocytes by TGFIII and TGFI2 was studied. In quiescent AKR-2B fibroblasts, in which TGFOi induces delayed stimulation of DNA synthesis, TGFII1 autoregulation of TGFI1 expression was observed as early as 1 h, with maximal induction (25-fold) after 6 to 12 h. Increased expression of TGF(II mRNA was accompanied by increased TGFO protein production into conditioned medium of AKR-2B cells. Neither TGFI32 nor TGFI3 mRNA, however, was significantly induced, but both were apparently down regulated at later times by TGFI31. Protein synthesis was not required for autoinduction of TGFfII mRNA in AKR-2B cells. Nuclear run-on analyses and dactinomycin experiments indicated that autoregulation of TGF(l expression is complex, involving both increased transcription and message stabilization. In contrast to TGF(11, TGFj32 treatment of quiescent AKR-2B cells increased expression of TGFI1, TGFI82, and TGF,3 mRNAs, but with different kinetics. Autoinduction of TGF,I2 mRNA occurred rapidly with maximal induction at 1 to 3 h, enhanced TGFI83 mRNA levels were observed after 3 h, and increased expression of TGFI1 occurred later, with maximal mRNA levels obtained after 12 to 24 h. Nuclear run-on analyses indicated that TGFI2 regulation of TGF,I2 and TGF,3 mRNA levels is transcriptional, while TGFP2 induction of TGFI{1 expression most likely involves both transcriptional and posttranscriptional controls. In BALB/MK mouse keratinocytes, minimal autoinduction of TGF(H occurred at only the 12-and 24-h time points and protein synthesis was required for this autoinduction. The results of this study provide an example in which TGFI1 and TGF,2 elicit different responses and demonstrate that expressions of TGFII1, TGF,I2, and TGFj13 are regulated differently. The physiological relevance of TGFIV1 autoinduction in the context of wound healing is discussed.