α3β1 integrin induced suppression of the Caco-2 epithelial cell IL-1 signaling pathway leading to NF-κB activation

Published on Sep 1, 2004in Cellular Immunology4.078
· DOI :10.1016/J.CELLIMM.2004.11.004
Gongchu Li9
Estimated H-index: 9
(Binghamton University),
Farah D. Lubin31
Estimated H-index: 31
(Binghamton University),
Dennis W. McGee13
Estimated H-index: 13
(Binghamton University)
Sources
Abstract
Abstract Intestinal epithelial cells (IECs) produce several potent cytokines in response to interleukin-1 (IL-1) and may play a role in the inflammatory response. Previously, we determined that treatment of the Caco-2 cells with a cross-linking anti-α3 integrin antibody resulted in a suppression of IL-1 induced cytokine secretion and mRNA levels, suggesting that the α3β1 integrin may play a role in the regulation of IEC cytokine responses to IL-1. In this report, treatment of the Caco-2 cells with the anti-α3 integrin antibody resulted in a suppression of IL-1 induced levels of NF-κB binding activity in nuclear extracts, as determined by EMSA, as well as phosphorylation and degradation of the inhibitor, IκBα. The anti-integrin antibody treatment was also found to suppress IκB kinase (IKK) activity and IKKβ phosphorylation. Culture of the Caco-2 cells on purified laminin-5, the ligand for the α3β1 integrin, also resulted in suppression of IL-1 induced phosphorylation of IκBα and IKKβ. Together with our previous findings, these results suggest that α3β1 integrin binding results in a suppression of the IL-1 signaling pathway leading to the activation of NF-κB and ultimately IEC cytokine responses. These studies define a novel regulatory mechanism which may be important in the control of IEC cytokine responses during inflammation.
📖 Papers frequently viewed together
10 Citations
75 Citations
200417.54Blood
135 Citations
References34
Newest
#1Farah D. Lubin (Binghamton University)H-Index: 31
#2Miriam Segal (Binghamton University)H-Index: 1
Last. Dennis W. McGee (Binghamton University)H-Index: 13
view all 3 authors...
Epithelial cells (EC) from various tissues can produce important cytokines and chemokines when stimulated by proinflammatory cytokines. These EC also receive signals from cell surface integrins, like the α3β1 integrin, which is important in cell migration and wound healing of epithelial monolayers. However, little is known of the effect of integrin signals on cytokine responses by EC. Colonic Caco-2 cells treated with an anti-α3 integrin antibody prior to stimulation with the proinflammatory cyt...
20 CitationsSource
#1Sharon Klein (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 11
#2Antonin R. de Fougerolles (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last. Filippo G. Giancotti (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 73
view all 8 authors...
GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the α5β1 integrin, but not to laminin through the α2β1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-κB transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-κB through a signaling pathway requiring Ras, phosphatidyl...
110 CitationsSource
Abstract In focal adhesions of eukaryotic cells, transmembrane receptors of the integrin family and a large set of adaptor proteins form the physical link between the extracellular substrate and the actin cytoskeleton. During cell migration, nascent focal adhesions within filopodia and lamellipodia make the initial exploratory contacts with the cellular environment, whereas maturing focal adhesions pull the cell forward against the resistance of ‘sliding' focal adhesions at the cell rear. Experi...
178 CitationsSource
#1R. L. Juliano (UNC: University of North Carolina at Chapel Hill)H-Index: 1
Cellular interactions with the extracellular matrix and with neighboring cells profoundly influence a variety of signaling events including those involved in mitogenesis, survival, and differentiation. Recent advances have provided insights into mechanisms underlying the ability of integrins, cadherins, selectins, and other cell adhesion molecules to regulate signal transduction cascades. These mechanisms often involve the ability of cell adhesion molecules to initiate the formation of organized...
525 CitationsSource
#1Beth P. Nguyen (Fred Hutchinson Cancer Research Center)H-Index: 2
#2Xiang-Dong Ren (Fred Hutchinson Cancer Research Center)H-Index: 8
Last. William G. Carter (Fred Hutchinson Cancer Research Center)H-Index: 40
view all 4 authors...
Abstract Wounding of the epidermis signals the transition of keratinocytes from quiescent anchorage on endogenous basement membrane laminin 5 to migration on exposed dermal collagen. In this study, we attempt to characterize activation signals that transform quiescent keratinocytes into migratory leading cells at the wound edge. Previously, we reported that adhesion and spreading on collagen via integrin α2β1 by cultured human foreskin keratinocytes (HFKs) requires RhoGTP, a regulator of actin s...
63 CitationsSource
#1Merit Reyes-ReyesH-Index: 3
#2Nancy Mora (UNAM: National Autonomous University of Mexico)H-Index: 9
Last. Carlos RosalesH-Index: 37
view all 4 authors...
Integrin-mediated signals play an important but poorly understood role in regulating many leukocyte functions. In monocytes and monocytic leukemia cells, (β)1 integrin-mediated adhesion results in a strong induction of immediate-early genes that are important in inflammation. To investigate the signaling pathways from integrins in monocytic cells, THP-1 cells were stimulated via (β)1 integrins by binding to fibronectin and by crosslinking the integrins with specific monoclonal antibodies. The in...
54 CitationsSource
#1Beth P. Nguyen (Fred Hutchinson Cancer Research Center)H-Index: 2
#2Maureen C Ryan (UW: University of Washington)H-Index: 1
Last. William G. Carter (UW: University of Washington)H-Index: 14
view all 4 authors...
Adhesion of keratinocytes in a wound outgrowth to laminin 5 in the basement membrane via integrins α6β4 and α3β1 is distinct from adhesion to dermal collagen via α2β1 or to fibronectin via α5β1. Leading cells in the outgrowth are distinguished from following keratinocytes by deposition of laminin 5, failure to communicate via gap junctions and sensitivity to toxin B, an inhibitor of RhoGTPase. Laminin 5 deposited by leading keratinocytes onto dermal collagen dominates over dermal ligands and cha...
225 CitationsSource
Abstract α3β1 integrin is a laminin receptor with apparently diverse functions. In epithelial cells it acts as a receptor for the basement membrane, whereas in neuronal and possibly tumor cells it mediates migration. Interactions of α3β1 integrin with tetraspanin proteins may provide clues to how it transduces signals that affect cell behavior.
164 CitationsSource
#1Christian Jobin (UNC: University of North Carolina at Chapel Hill)H-Index: 75
#2R. Balfour Sartor (UNC: University of North Carolina at Chapel Hill)H-Index: 81
The ubiquitous transcription factor NF-κB is a central regulator of the transcriptional activation of a number of genes involved in cell adhesion, immune and proinflammatory responses, apoptosis, d...
311 CitationsSource
#1Lawrence E. Goldfinger (NU: Northwestern University)H-Index: 6
#2Susan B. HopkinsonH-Index: 27
Last. Jonathan C.R. JonesH-Index: 69
view all 6 authors...
Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 s...
240 CitationsSource
Cited By12
Newest
#1Yudan Wang (NCU: Nanchang University)H-Index: 2
#2Xiaomeng Ding (NCU: Nanchang University)H-Index: 3
Last. Qiang Yu (NCU: Nanchang University)H-Index: 21
view all 9 authors...
Abstract The previous research has indicated that Ganoderma atrum polysaccharide (PSG-1) indirectly affects the immune function of dendritic cells (DCs) in intestinal-like Caco-2/DCs co-culture model, in which NF-κB and MAPK pathway play an essential role. To explore the interaction of Caco-2 in the interaction between the intestinal epithelium and its internal immune cells, the intestinal-like Caco-2/DCs co-culture model was developed. All transcripts of Caco-2 treated with or without PSG-1 wer...
1 CitationsSource
#1Rui Zheng (Albany Medical College)H-Index: 3
#2Whitney M. Longmate (Albany Medical College)H-Index: 7
Last. Livingston Van De Water (Albany Medical College)H-Index: 17
view all 7 authors...
After cutaneous injury, keratinocytes secrete paracrine factors that regulate wound cell functions; dysregulation of this signaling can lead to wound pathologies. Previously, we established that keratinocyte integrin α3β1 promotes wound angiogenesis through paracrine stimulation of endothelial cells. We hypothesize here that α3β1-dependent paracrine signaling from keratinocytes regulates the differentiation state of myofibroblasts. We report that epidermal α3-knockout mice exhibit more wound myo...
8 CitationsSource
#1Brian Rafferty (Binghamton University)H-Index: 6
#2Benjamin L. Unger (Binghamton University)H-Index: 3
Last. Dennis W. McGee (Binghamton University)H-Index: 13
view all 6 authors...
Intestinal epithelial cells (IEC) play a role in mucosal inflammation by producing pro-inflammatory chemokines that may initiate or amplify local responses. IL-1 is a potent activator of IEC and its receptor localizes to focal adhesions. Since the Rho-associated kinase, ROCK, also localizes to focal adhesions, we examined the role of ROCK in IL-1-induced chemokine responses in IEC cell lines. Suppressing ROCK with the Y27632 inhibitor suppressed IL-1-stimulated Caco-2 cell CXCL8/IL-8 and IEC-6 c...
11 CitationsSource
#1Caroline Spenlé (French Institute of Health and Medical Research)H-Index: 15
#2Thomas Hussenet (UDS: University of Strasbourg)H-Index: 14
Last. Patricia Simon-Assmann (UDS: University of Strasbourg)H-Index: 49
view all 7 authors...
Abstract Laminins are structural components of basement membranes that regulate and control many cellular functions. Changes in basement membrane composition play significant roles in etiology of diseases. Inflammatory bowel diseases are conditions that lead to defects in the mucosal barrier which includes the basement membrane underlying the epithelium. This review will summarize the main findings related to the involvement of laminins and of the laminin-binding receptors in inflammatory condit...
16 CitationsSource
#1Brian Rafferty (Binghamton University)H-Index: 6
#2Gongchu Li (Binghamton University)H-Index: 9
Last. Dennis W. McGee (Binghamton University)H-Index: 13
view all 3 authors...
Intestinal epithelial cells express the α3β1 integrin which binds to laminin-5. We have previously shown that activation of the α3 integrin through laminin-5 binding or a cross-linking antibody results in a suppression of IL-1 induced cytokine secretion and intracellular signaling through IKK to NF-κB and JNK to AP-1 in Caco-2 cells. In the present study, the effects of α3 integrin activation on the proximal events of IL-1 induced signaling were examined. Monoclonal antibody activation of the α3...
1 CitationsSource
#1Dongkyun Kim (UPR-RP: UPRRP College of Natural Sciences)H-Index: 16
#2Song Ja Kim (UPR-RP: UPRRP College of Natural Sciences)H-Index: 27
Last. Eun-Jung Jin (UPR-RP: UPRRP College of Natural Sciences)H-Index: 23
view all 4 authors...
Curcumin is a well known natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown. In the present report, we investigated the effects and signaling mechanism of cur...
10 CitationsSource
#1Ewa KarnaH-Index: 15
#2Wojciech MiltykH-Index: 19
Last. Jerzy PałkaH-Index: 26
view all 4 authors...
The mechanism of protective action of hyaluronic acid (HA) on collagen metabolism disturbances in tissues during inflammation is not known. Insulin-like growth factor-I (IGF-I) receptor and β1-integrin receptor signaling plays an important role in the regulation of collagen biosynthesis at both transcriptional and post-transcriptional levels. The present study was undertaken to evaluate the effect of IL-1β (inductor of experimental inflammation) on the signaling pathways as well as on collagen b...
27 CitationsSource
#1Mate Stulic (Binghamton University)H-Index: 1
#2Farah D. Lubin (Binghamton University)H-Index: 31
Last. Dennis W. McGee (Binghamton University)H-Index: 13
view all 5 authors...
Abstract Intestinal epithelial cells (IEC) are capable of responding to IL-1 stimulation by producing a variety of pro-inflammatory cytokines. Recently, we have found that binding of the α3β1 integrin may have a regulatory effect on IL-1 responses and intracellular signaling by suppressing cytokine secretion, mRNA expression and the downstream intracellular signaling events from IKK to NF-κB activation. In this study, we extend these findings by showing that treatment of the Caco-2 epithelial ce...
6 CitationsSource
#1Ewa KarnaH-Index: 15
#2Wojciech MiltykH-Index: 19
Last. Slawomir WolczynskiH-Index: 30
view all 5 authors...
Abstract Although, hyaluronic acid (HA) is used in the treatment of osteoarthritis for 30 years, the mechanism of its protective action on collagen metabolism disturbances in tissues during inflammation is not known. Therefore, the present study was undertaken to evaluate the mechanism of IL-1β action (inductor of experimental inflammation) on deregulation of collagen biosynthesis in cultured human chondrocytes and the effect of HA on the process. It has been found that IL-1β strongly induced in...
37 CitationsSource