Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1

Naeem A. Ali; Alice A. Gaughan; Charles G. Orosz; Chris P. Baran; Sara McMaken; Yijie Wang; Timothy D. Eubank; Melissa Hunter; Frank J. Lichtenberger; Nicholas A. Flavahan; Jack Lawler; Clay B. Marsh

doi:10.1371/journal.pone.0001914

Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1

Naeem A. Ali, Alice A. Gaughan, Charles G. Orosz, Chris P. Baran, Sara McMaken, Yijie Wang, Timothy D. Eubank, Melissa Hunter, Frank J. Lichtenberger, Nicholas A. Flavahan, Jack Lawler, Clay B. Marsh

School of Medicine

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work show that LAP can induce epithelial cell migration, but effect on leukocyte have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune response. In separate experiments we found that LAP promoted chemotaxis opf human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-B1 activity. Further studies revealed that disruption of specific LAP thrombospondin-1 (TSP-1) interactions prevented LAP induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation.

Original language	English (US)
Article number	e1914
Journal	PloS one
Volume	3
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0001914
State	Published - Apr 2 2008

ASJC Scopus subject areas

General

Access to Document

10.1371/journal.pone.0001914

Cite this

@article{aa7337deb75d43fca1387b9e94147375,

title = "Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1",

abstract = "Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work show that LAP can induce epithelial cell migration, but effect on leukocyte have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune response. In separate experiments we found that LAP promoted chemotaxis opf human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-B1 activity. Further studies revealed that disruption of specific LAP thrombospondin-1 (TSP-1) interactions prevented LAP induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation.",

author = "Ali, {Naeem A.} and Gaughan, {Alice A.} and Orosz, {Charles G.} and Baran, {Chris P.} and Sara McMaken and Yijie Wang and Eubank, {Timothy D.} and Melissa Hunter and Lichtenberger, {Frank J.} and Flavahan, {Nicholas A.} and Jack Lawler and Marsh, {Clay B.}",

year = "2008",

month = apr,

day = "2",

doi = "10.1371/journal.pone.0001914",

language = "English (US)",

volume = "3",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "4",

}

TY - JOUR

T1 - Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1

AU - Ali, Naeem A.

AU - Gaughan, Alice A.

AU - Orosz, Charles G.

AU - Baran, Chris P.

AU - McMaken, Sara

AU - Wang, Yijie

AU - Eubank, Timothy D.

AU - Hunter, Melissa

AU - Lichtenberger, Frank J.

AU - Flavahan, Nicholas A.

AU - Lawler, Jack

AU - Marsh, Clay B.

PY - 2008/4/2

Y1 - 2008/4/2

N2 - Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work show that LAP can induce epithelial cell migration, but effect on leukocyte have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune response. In separate experiments we found that LAP promoted chemotaxis opf human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-B1 activity. Further studies revealed that disruption of specific LAP thrombospondin-1 (TSP-1) interactions prevented LAP induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation.

AB - Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work show that LAP can induce epithelial cell migration, but effect on leukocyte have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune response. In separate experiments we found that LAP promoted chemotaxis opf human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-B1 activity. Further studies revealed that disruption of specific LAP thrombospondin-1 (TSP-1) interactions prevented LAP induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation.

UR - http://www.scopus.com/inward/record.url?scp=44849129542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44849129542&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0001914

DO - 10.1371/journal.pone.0001914

M3 - Article

C2 - 18392110

AN - SCOPUS:44849129542

SN - 1932-6203

VL - 3

JO - PloS one

JF - PloS one

IS - 4

M1 - e1914

ER -

Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this