Influence of Kupffer cells on hepatic signal transduction as demonstrated by second messengers and nuclear transcription factors.

AIM: To understand the influence of Kupffer cell (KC) on signal transduction pathways in the liver. METHODS: To decrease selectively the number and function of KC, Kunming mice were ip injected with a single dose of gadolinium chloride (GdCl3, 20 mg x kg(-1)), the time-effect relationship assessment was performed after 1 d, 3 d and 6 d. sALT, sGST, liver glycogen content, phagocytic index, and expression of CD68 were assessed as the indexes of hepatotoxicity and functions of KC respectively, and morphology of KC was observed with transmission electron microscopy. Furthermore, cAMP, PGE2 level, nitric oxide (NO) content, and mRNA expression of NFkappaBp65, Erk1, STAT1 were examined. RESULTS: GdCl3 could selectively cause apoptosis of KC and obvious reduction of KC's activity, but no hepatotoxicity was observed. One day after KC blockade, NO, PGE2, cAMP contents in the liver were reduced 21.0%, 6.94-fold, 8.3%, respectively, and mRNA expression of NFkappaBp65 was decreased 3.0-fold. The change tendency of NO, PGE2, and cAMP contents and mRNA expression of NFkappaBp65 were concomitant with recovery of the functions of KC. The contents of NO, PEG2, cAMP were increased when the functions of KC was recovered. However, all of the changes could not return to the normal level except NO content after 6 d Gdcl3 treatment. No obvious changes were found in STAT1 and Erk1 mRNA expression in the present study. CONCLUSION: Hepatic NO, PGE2, cAMP level and mRNA expression of NFkappaBp65 are closely related with the status of KC. It suggests that KC may play an important role in the cell to cell signal transduction in the liver.