|
|
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = M;code = 77
char = 2;code = 50
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char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
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char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
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char = i;code = 105
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char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
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char = k;code = 107
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = y;code = 121
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char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
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char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
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char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = l;code = 108
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.
TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.char = R;code = 82
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char = a;code = 97
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char = t;code = 116
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char = ;code = 32
char = o;code = 111
char = x;code = 120
char = y;code = 121
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char = e;code = 101
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = k;code = 107
char = i;code = 105
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char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
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char = i;code = 105
char = b;code = 98
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char = o;code = 111
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char = t;code = 116
char = h;code = 104
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = r;code = 114
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char = i;code = 105
char = t;code = 116
char = m;code = 109
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char = n;code = 110
char = t;code = 116
char = ;code = 32
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char = m;code = 109
char = a;code = 97
char = t;code = 116
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char = y;code = 121
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
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char = j;code = 106
char = u;code = 117
char = r;code = 114
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char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
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char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
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char = C;code = 67
char = a;code = 97
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char = 2;code = 50
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char = p;code = 112
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char = r;code = 114
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char = a;code = 97
char = b;code = 98
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char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = M;code = 77
char = 2;code = 50
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char = c;code = 99
char = o;code = 111
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char = r;code = 114
char = o;code = 111
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = R;code = 82
char = O;code = 79
char = S;code = 83
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = d;code = 100
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char = c;code = 99
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char = k;code = 107
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char = n;code = 110
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char = i;code = 105
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char = .;code = 46
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char = m;code = 109
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char = U;code = 85
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char = ,;code = 44
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char = (;code = 40
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char = 2;code = 50
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char = (;code = 40
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char = );code = 41
char = );code = 41
char = ;code = 32
char = e;code = 101
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char = o;code = 111
char = k;code = 107
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
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char = +;code = 43
char = );code = 41
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char = i;code = 105
char = n;code = 110
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char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = t;code = 116
char = h;code = 104
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char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = T;code = 84
char = R;code = 82
char = P;code = 80
char = M;code = 77
char = 2;code = 50
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = c;code = 99
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char = i;code = 105
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char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
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char = );code = 41
char = -;code = 45
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = r;code = 114
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char = n;code = 110
char = e;code = 101
char = ;code = 32
char = k;code = 107
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char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = P;code = 80
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char = k;code = 107
char = 2;code = 50
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char = a;code = 97
char = n;code = 110
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char = ;code = 32
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = y;code = 121
char = ;code = 32
char = E;code = 69
char = r;code = 114
char = k;code = 107
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = G;code = 71
char = T;code = 84
char = P;code = 80
char = a;code = 97
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char = e;code = 101
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char = T;code = 84
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char = ;code = 32
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char = l;code = 108
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char = t;code = 116
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char = c;code = 99
char = l;code = 108
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char = a;code = 97
char = r;code = 114
char = ;code = 32
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char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = c;code = 99
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char = f;code = 102
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char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = e;code = 101
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char = s;code = 115
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char = m;code = 109
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char = T;code = 84
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char = C;code = 67
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char = C;code = 67
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char = l;code = 108
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char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
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char = t;code = 116
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char = r;code = 114
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char = p;code = 112
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char = p;code = 112
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result sql = Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evokes Ca(2+) influx through TRPM2 to activate Ca(2+)-dependent tyrosine kinase Pyk2 and amplify Erk signaling via Ras GTPase. This elicits nuclear translocation of nuclear factor-kappaB essential for the production of the chemokine interleukin-8 (CXCL8). In monocytes from Trpm2-deficient mice, H(2)O(2)-induced Ca(2+) influx and production of the macrophage inflammatory protein-2 (CXCL2), the mouse CXCL8 functional homolog, were impaired. In the dextran sulfate sodium-induced colitis inflammation model, CXCL2 expression, neutrophil infiltration and ulceration were attenuated by Trpm2 disruption. Thus, TRPM2 Ca(2+) influx controls the ROS-induced signaling cascade responsible for chemokine production, which aggravates inflammation. We propose functional inhibition of TRPM2 channels as a new therapeutic strategy for treating inflammatory diseases.
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char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
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char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
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char = i;code = 105
char = n;code = 110
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char = u;code = 117
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char = e;code = 101
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char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = m;code = 109
char = o;code = 111
char = k;code = 107
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char = n;code = 110
char = e;code = 101
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char = p;code = 112
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char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
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char = i;code = 105
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char = m;code = 109
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char = a;code = 97
char = t;code = 116
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char = i;code = 105
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char = m;code = 109
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char = o;code = 111
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char = e;code = 101
char = u;code = 117
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = l;code = 108
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.
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result sql = Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evokes Ca(2+) influx through TRPM2 to activate Ca(2+)-dependent tyrosine kinase Pyk2 and amplify Erk signaling via Ras GTPase. This elicits nuclear translocation of nuclear factor-kappaB essential for the production of the chemokine interleukin-8 (CXCL8). In monocytes from Trpm2-deficient mice, H(2)O(2)-induced Ca(2+) influx and production of the macrophage inflammatory protein-2 (CXCL2), the mouse CXCL8 functional homolog, were impaired. In the dextran sulfate sodium-induced colitis inflammation model, CXCL2 expression, neutrophil infiltration and ulceration were attenuated by Trpm2 disruption. Thus, TRPM2 Ca(2+) influx controls the ROS-induced signaling cascade responsible for chemokine production, which aggravates inflammation. We propose functional inhibition of TRPM2 channels as a new therapeutic strategy for treating inflammatory diseases.
Publication: Nat. Med. 2008 Jul ;14(7)::738-47. :doi: 10.1038/nm1758.
Publication Date: 2008 Jul
Study Author(s): Yamamoto, Shinichiro;Shimizu, Shunichi;Kiyonaka, Shigeki;Takahashi, Nobuaki;Wajima, Teruaki;Hara, Yuji;Negoro, Takaharu;Hiroi, Toshihito;Kiuchi, Yuji;Okada, Takaharu;Kaneko, Shuji;Lange, Ingo;Fleig, Andrea;Penner, Reinhold;Nishi, Miyuki;Takeshima, Hiroshi;Mori, Yasuo;
Institution: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan.
Shortcut link to this study:
Publication Date: 2008 Jul
Study Author(s): Yamamoto, Shinichiro;Shimizu, Shunichi;Kiyonaka, Shigeki;Takahashi, Nobuaki;Wajima, Teruaki;Hara, Yuji;Negoro, Takaharu;Hiroi, Toshihito;Kiuchi, Yuji;Okada, Takaharu;Kaneko, Shuji;Lange, Ingo;Fleig, Andrea;Penner, Reinhold;Nishi, Miyuki;Takeshima, Hiroshi;Mori, Yasuo;
Institution: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan.
Shortcut link to this study:
Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evokes Ca(2+) influx through TRPM2 to activate Ca(2+)-dependent tyrosine kinase Pyk2 and amplify Erk signaling via Ras GTPase. This elicits nuclear translocation of nuclear factor-kappaB essential for the production of the chemokine interleukin-8 (CXCL8). In monocytes from Trpm2-deficient mice, H(2)O(2)-induced Ca(2+) influx and production of the macrophage inflammatory protein-2 (CXCL2), the mouse CXCL8 functional homolog, were impaired. In the dextran sulfate sodium-induced colitis inflammation model, CXCL2 expression, neutrophil infiltration and ulceration were attenuated by Trpm2 disruption. Thus, TRPM2 Ca(2+) influx controls the ROS-induced signaling cascade responsible for chemokine production, which aggravates inflammation. We propose functional inhibition of TRPM2 channels as a new therapeutic strategy for treating inflammatory diseases.
PMID: 18542050
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