A common pathway in differentiation and inflammation: p38 mediates expression of the acute phase SIP24 iron binding lipocalin in chondrocytes

• Published in: Journal of cellular physiology Vol. 206; no. 3; pp. 728 - 737
• Main Authors: Ulivi, Valentina, Tutolo, Giorgia, Mallein-Gerin, Frédéric, Daga, Antonio, Cancedda, Ranieri, Cancedda, Fiorella Descalzi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2006; Wiley
• Subjects: Acute-Phase Proteins - biosynthesis; Acute-Phase Proteins - genetics; Acute-Phase Proteins - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; Biochemistry, Molecular Biology; Cartilage - embryology; Cell Differentiation; Cell Line; Cell Proliferation; Chondrocytes - metabolism; Cytokines - pharmacology; Inflammation - metabolism; Iron - metabolism; Life Sciences; Lipocalin-2; Lipocalins; Mice; Models, Biological; NF-kappa B - metabolism; NF-kappa B - physiology; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases - physiology; Protein Kinase C - metabolism; Signal Transduction
• DOI: 10.1002/jcp.20511
• ISSN: 0021-9541

SIP24 is an acute phase iron binding lipocalin physiologically expressed in vivo in developing cartilage by prehypertrophic/hypertrophic chondrocytes. Taking advantage of the chondrocytic cell line MC615 and using SIP24 as a marker we investigated the pathways active in cartilage differentiation and inflammation. MC615 cells were cultured as: (i) proliferating prechondrogenic cells expressing type I collagen (ii) differentiated hyperconfluent cells expressing Sox9 and type II collagen. In proliferating cells the pathway PKC/ERK1, ERK2 was activated and SIP24 was not expressed while in differentiated cells the pathway p38/NF‐κB was activated and SIP24 was expressed. Proliferating cells treated with inflammatory agents expressed a large amount of SIP24 and showed activation of p38/NF‐κB pathway and inhibition of PKC/ERK1, ERK2 pathway indicating that in inflammation and differentiation the same factors are activated (p38, NF‐κB) or inactivated (PKC, ERKs). Treatment of proliferating cells with the p38 specific inhibitor SB203580 inhibited the inflammation induced activation of p38 and the synthesis of SIP24. PMA treatment induced activation of PKC, inactivation of p38 and suppression of SIP24 synthesis, suggesting that PKC activation inhibits p38 activation. In differentiated hyperconfluent cells the same factors (p38/NF‐κB/SIP24) are constitutively activated: treatment with inflammatory agents does not increase synthesis of SIP24 while treatment with SB203580 and with PMA does not repress activation of p38 nor synthesis of SIP24. We propose that the SIP24 stress related protein is expressed via p38 activation/NF‐κB recruitment both in chondrocyte differentiation and inflammation and that a signaling pathway active in the acute phase response is physiologically activated in differentiation. © 2005 Wiley‐Liss, Inc.