Interleukin-1β Gene Transcription in U937 Cells Is Modulated by Type I Collagen and Cytoskeletal Integrity via Distinct Signaling Pathways

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Abstract
Type I collagen (Col), an extracellular matrix molecule highly expressed in injured tissues, stimulates interleukin-1β (IL-1β) expression in monocytic cells. Using U937 cells transfected with the human IL-1β gene promoter connected to a reporter gene, we examined how the organizational state of the cytoskeleton modulates the expression of IL-1β after Col stimulation. We found the same degree of stimulation of IL-1β gene transcription in cells exposed to Col presented in different fashions (i.e., soluble Col, Col-coated plate, three-dimensional Col lattice), suggesting that stimulation of IL-1β is independent of the mode of presentation of Col. The Col-stimulated response was associated with induction of the transcription factor activator protein-1 (AP-1) and was abolished by a protein kinase C (PKC) inhibitor, by a mitogen-activated protein kinase (MAPK) inhibitor, and by cotransfection of cells with a competing AP-1 oligo. Disruption of cytoskeletal organization with colchicine or cytochalasin B stimulated IL-1β gene transcription and enhanced the cells' response to Col. The effects of cytochalasin and cochicine were inhibited by the PKC inhibitor but were not affected by the MAPK inhibitor or the AP-1 oligo. These findings suggest that the cytoskeletal integrity modulates the constitutive and Col-stimulated transcription of the IL-1β gene via distinct signaling mechanisms.

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