Characterization of tissue transglutaminase 2 in macrophage function

Vinod Nadella, Vivian Wang, Martin Griffin, Andrew Devitt

Research output: Contribution to conferencePoster

Abstract

Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.
LanguageEnglish
Pages74
Number of pages1
Publication statusPublished - 2012
EventBritish Society for Research on Ageing - Birmingham, United Kingdom
Duration: 2 Jul 20124 Jul 2012

Conference

ConferenceBritish Society for Research on Ageing
CountryUnited Kingdom
CityBirmingham
Period2/07/124/07/12

Fingerprint

Macrophages
Syndecan-4
Guanosine Triphosphate
transglutaminase 2
Proteins
Cell Aging
Enzymes
Keratinocytes
Integrins
Cell Communication
Cataract
Compliance
Blood Vessels
Cell Differentiation
Signal Transduction
Cell Cycle
Alzheimer Disease
Carcinogenesis
Arteries
Cell Proliferation

Cite this

Nadella, V., Wang, V., Griffin, M., & Devitt, A. (2012). Characterization of tissue transglutaminase 2 in macrophage function. 74. Poster session presented at British Society for Research on Ageing, Birmingham, United Kingdom.
Nadella, Vinod ; Wang, Vivian ; Griffin, Martin ; Devitt, Andrew. / Characterization of tissue transglutaminase 2 in macrophage function. Poster session presented at British Society for Research on Ageing, Birmingham, United Kingdom.1 p.
@conference{f8f866c33dcf4a979de6de8fba2e08ff,
title = "Characterization of tissue transglutaminase 2 in macrophage function",
abstract = "Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and {\ss}3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.",
author = "Vinod Nadella and Vivian Wang and Martin Griffin and Andrew Devitt",
year = "2012",
language = "English",
pages = "74",
note = "British Society for Research on Ageing ; Conference date: 02-07-2012 Through 04-07-2012",

}

Nadella, V, Wang, V, Griffin, M & Devitt, A 2012, 'Characterization of tissue transglutaminase 2 in macrophage function' British Society for Research on Ageing, Birmingham, United Kingdom, 2/07/12 - 4/07/12, pp. 74.

Characterization of tissue transglutaminase 2 in macrophage function. / Nadella, Vinod; Wang, Vivian; Griffin, Martin; Devitt, Andrew.

2012. 74 Poster session presented at British Society for Research on Ageing, Birmingham, United Kingdom.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Characterization of tissue transglutaminase 2 in macrophage function

AU - Nadella, Vinod

AU - Wang, Vivian

AU - Griffin, Martin

AU - Devitt, Andrew

PY - 2012

Y1 - 2012

N2 - Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.

AB - Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.

M3 - Poster

SP - 74

ER -

Nadella V, Wang V, Griffin M, Devitt A. Characterization of tissue transglutaminase 2 in macrophage function. 2012. Poster session presented at British Society for Research on Ageing, Birmingham, United Kingdom.