Multifactorial induction of gene expression and nuclear localization of mouse interleukin 1 alpha.

We have studied mouse brown adipose tissue (BAT) which was shown to contain high levels of mRNA for IL-1 alpha and IL-1 receptor. We found high contents of both the 31 kDa precursor and the 18 kDa mature form of IL-1 alpha proteins in BAT when compared with brain, lymph nodes and spleen. Both forms of IL-1 alpha were also present in primary cultures of BAT. The IL-1 alpha subcellular localization revealed the predominant nuclear association of both precursor and mature form of IL-1 alpha which accounted for 48% of total cellular IL-1 alpha in BAT and a similar subcellular distribution was found in spleen. The specific content of IL-1 alpha found in nuclei purified from BAT or from cultured brown adipocytes was 6-47-fold higher than in other cellular fractions. Nuclear IL-1 alpha was increased by addition of 10% fetal calf serum to cultured adipocytes previously depleted of the serum. The expression of the IL-1A gene in cultured brown adipocytes was increased 6-8-fold by IL-1 beta, TNF-alpha, LPS and by noradrenaline. The stimulation with all four agents, resulted in a rapid burst of IL-1 alpha mRNA level after 15-30 min. The highest stimulation was found in differentiated, preconfluent adipocytes cultured for 6 days. The results suggest an important regulatory role of IL-1 alpha in brown adipocytes. The rapid responses of IL-1A gene expression to multifactorial stimulation and pronounced nuclear localization of IL-1 alpha proteins further support the existence of a hypothetical nuclear function of IL-1 alpha.