Paradoxical preservation of a lipopolysaccharide response in C3H/HeJ macrophages: Induction of matrix metalloproteinase-9

C3H/HeJ mice carry a mutant allele (Lps(d)) of a recently identified gene w hose normal allele (Lps(n)) confers responsiveness to bacterial LPS in C3H/ HeN and most other mouse strains. Recently we reported a differential displ ay analysis of matched macrophage-derived cell lines from C3H/HeJ and C3H/H eN mice under LPS-free conditions. Of the similar to 12,000 transcripts eva luated, 4 were differentially expressed. One transcript represented secreto ry leukocyte protease inhibitor. In this study, we report another different ially expressed transcript, mouse matrix metalloprotease-9 (MMF-9). Like se cretory leukocyte protease inhibitor, MMP-9 was expressed constitutively in the Lpsd macrophage cell line and not in the Lps(n) cell line. Similarly, two additional macrophage cell lines that respond readily to LPS by produci ng nitric oxide and TNF expressed no MMP-9 under LPS-free conditions. Howev er, in all four cell lines, LPS induced MMP-9 or augmented its expression. In primary macrophages, concentrations of LPS in the ng/ml range augmented the expression of MMP-9 mRNA, Paradoxically, macrophages from Lps(d) mice e xpressed more MMP-9 transcripts than macrophages from Lps(n) mice. In contr ast, the induction of TNF in response to LPS was much mure pronounced in Lp s(n) macrophages, The present findings with MMP-9 suggest that homozygosity at Lps(d) does not so much prevent a response to LPS as dysregulate it, re sulting in the suppression of some LPS signaling pathways and the preservat ion of others.