Abstract
Background and purpose: Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR. Experimental approach: Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-γ, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [3H]-thymidine uptake. Key results: Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H2-receptor antagonist, famotidine, and mimicked by H2/H4-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. Conclusions and implications: Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H2 receptors and the cAMP/PKA pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 1378-1386 |
| Number of pages | 9 |
| Journal | British Journal of Pharmacology |
| Volume | 160 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2010 |
Fingerprint
Keywords
- adhesion molecule
- advanced glycation end products
- cyclic adenosine monophosphate
- diabetes
- histamine
- human mixed lymphocyte reaction
- monocytes
- transplantation
ASJC Scopus subject areas
- Pharmacology
- Medicine(all)
Cite this
Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction. / Zhang, J.; Takahashi, H. K.; Liu, K.; Wake, Hidenori; Liu, R.; Sadamori, H.; Matsuda, H.; Yagi, Takahito; Yoshino, Tadashi; Mori, S.; Nishibori, Masahiro.
In: British Journal of Pharmacology, Vol. 160, No. 6, 2010, p. 1378-1386.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction
AU - Zhang, J.
AU - Takahashi, H. K.
AU - Liu, K.
AU - Wake, Hidenori
AU - Liu, R.
AU - Sadamori, H.
AU - Matsuda, H.
AU - Yagi, Takahito
AU - Yoshino, Tadashi
AU - Mori, S.
AU - Nishibori, Masahiro
PY - 2010
Y1 - 2010
N2 - Background and purpose: Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR. Experimental approach: Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-γ, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [3H]-thymidine uptake. Key results: Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H2-receptor antagonist, famotidine, and mimicked by H2/H4-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. Conclusions and implications: Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H2 receptors and the cAMP/PKA pathway.
AB - Background and purpose: Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR. Experimental approach: Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-γ, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [3H]-thymidine uptake. Key results: Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H2-receptor antagonist, famotidine, and mimicked by H2/H4-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. Conclusions and implications: Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H2 receptors and the cAMP/PKA pathway.
KW - adhesion molecule
KW - advanced glycation end products
KW - cyclic adenosine monophosphate
KW - diabetes
KW - histamine
KW - human mixed lymphocyte reaction
KW - monocytes
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=77954079853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954079853&partnerID=8YFLogxK
U2 - 10.1111/j.1476-5381.2010.00800.x
DO - 10.1111/j.1476-5381.2010.00800.x
M3 - Article
VL - 160
SP - 1378
EP - 1386
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 6
ER -