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result sql = Use of IL-8 release and p38 MAPK activation in THP-1 cells to identify allergens and to assess their potency in vitro.
Use of IL-8 release and p38 MAPK activation in THP-1 cells to identify allergens and to assess their potency in vitro.
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char = l;code = 108
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char = e;code = 101
char = ;code = 32
char = e;code = 101
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char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
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char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
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char = b;code = 98
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char = n;code = 110
char = z;code = 122
char = o;code = 111
char = q;code = 113
char = u;code = 117
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char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = ;code = 32
char = 2;code = 50
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char = a;code = 97
char = m;code = 109
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char = n;code = 110
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = u;code = 117
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = t;code = 116
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char = y;code = 121
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char = ;code = 32
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = z;code = 122
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = o;code = 111
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char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = L;code = 76
char = L;code = 76
char = N;code = 78
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = y;code = 121
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = F;code = 70
char = A;code = 65
char = C;code = 67
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 8;code = 56
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = E;code = 69
char = L;code = 76
char = I;code = 73
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = b;code = 98
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = t;code = 116
char = a;code = 97
char = c;code = 99
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char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
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char = g;code = 103
char = e;code = 101
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = e;code = 101
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char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = e;code = 101
char = u;code = 117
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 8;code = 56
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
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char = l;code = 108
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
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char = g;code = 103
char = e;code = 101
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char = s;code = 115
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char = t;code = 116
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char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = i;code = 105
char = s;code = 115
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char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
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char = u;code = 117
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
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char = b;code = 98
char = e;code = 101
char = ;code = 32
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char = u;code = 117
char = e;code = 101
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char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = f;code = 102
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 8;code = 56
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char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = a;code = 97
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char = p;code = 112
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char = b;code = 98
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char = h;code = 104
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char = p;code = 112
char = 3;code = 51
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char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = a;code = 97
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char = v;code = 118
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char = I;code = 73
char = L;code = 76
char = -;code = 45
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char = r;code = 114
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char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = g;code = 103
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char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
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char = e;code = 101
char = n;code = 110
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char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 8;code = 56
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char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = L;code = 76
char = L;code = 76
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = f;code = 102
char = o;code = 111
char = u;code = 117
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char = ;code = 32
char = (;code = 40
char = P;code = 80
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
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char = 0;code = 48
char = .;code = 46
char = 7;code = 55
char = 4;code = 52
char = 3;code = 51
char = ,;code = 44
char = ;code = 32
char = p;code = 112
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char = .;code = 46
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char = 0;code = 48
char = 3;code = 51
char = 6;code = 54
char = ,;code = 44
char = ;code = 32
char = n;code = 110
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char = 1;code = 49
char = 2;code = 50
char = );code = 41
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = o;code = 111
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = r;code = 114
char = y;code = 121
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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result sql = The local lymph node assay (LLNA) has been developed to assess skin sensitization, and based on the EC3 value, it can also be used to evaluate allergen potency. Therefore, in the development of in vitro alternatives to the LLNA assay, one should not only consider the hazard identification but also the possibility to classify allergens relatively to their potency. We have recently described a selective release of interleukin-8 (IL-8) by chemical allergens in THP-1 cell line, and identified the activation of p38 mitogen-activated protein kinase (p38 MAPK) as a common pathway. Therefore, the purpose of this study was to expand the number of chemicals tested and to investigate whether IL-8 production and p38 MAPK activation can be used to classify allergens according to their potency. THP-1 cells were exposed to the contact allergens (p-benzoquinone, 2-aminophenol, isoeugenol, diethyl maleate, citral and imidazolidinyl urea), selected according to their potency in the LLNA, and to lactic acid and propylene glycol as non-sensitizers. p38 MAPK activation was evaluated 5-15 min after treatment by FACS analysis, while IL-8 release was assed by ELISA following 24h of incubation. p38 MAPK was activated by all contact allergens, including the pro-apten isoeugenol, whereas IL-8 release was significantly increased after stimulation with all allergens tested, except for isoeugenol. The failure of isoeugenol may be due to decrease in the stability of IL-8 mRNA. Irritants exposure, as expected, failed to induce both p38 MAPK activation and IL-8 release. A significant correlation between IL-8 release and the LLNA EC(3) was found (Pearson correlation r=0.743, p=0.0036, n=12). On the contrary, the activation of p38 MAPK showed no significant correlation between LLNA data and vigor of p38 MAPK activation. Overall, data presented confirm our previous observations and reveal IL-8 as potential tool not only to identify sensitizers, with the exception of pro-haptens, but also to classify them according to their potency, while p38 MAPK activation allows the identification of all sensitizers, including pro-haptens, but was not useful for potency classification.

Publication: Toxicol In Vitro 2010 Sep ;24(6)::1803-9. :doi: 10.1016/j.tiv.2010.06.001.
Publication Date: 2010 Sep
Study Author(s): Mitjans, M;Galbiati, V;Lucchi, L;Viviani, B;Marinovich, M;Galli, C L;Corsini, E;
Institution: Departamento Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Shortcut link to this study:
The local lymph node assay (LLNA) has been developed to assess skin sensitization, and based on the EC3 value, it can also be used to evaluate allergen potency. Therefore, in the development of in vitro alternatives to the LLNA assay, one should not only consider the hazard identification but also the possibility to classify allergens relatively to their potency. We have recently described a selective release of interleukin-8 (IL-8) by chemical allergens in THP-1 cell line, and identified the activation of p38 mitogen-activated protein kinase (p38 MAPK) as a common pathway. Therefore, the purpose of this study was to expand the number of chemicals tested and to investigate whether IL-8 production and p38 MAPK activation can be used to classify allergens according to their potency. THP-1 cells were exposed to the contact allergens (p-benzoquinone, 2-aminophenol, isoeugenol, diethyl maleate, citral and imidazolidinyl urea), selected according to their potency in the LLNA, and to lactic acid and propylene glycol as non-sensitizers. p38 MAPK activation was evaluated 5-15 min after treatment by FACS analysis, while IL-8 release was assed by ELISA following 24h of incubation. p38 MAPK was activated by all contact allergens, including the pro-apten isoeugenol, whereas IL-8 release was significantly increased after stimulation with all allergens tested, except for isoeugenol. The failure of isoeugenol may be due to decrease in the stability of IL-8 mRNA. Irritants exposure, as expected, failed to induce both p38 MAPK activation and IL-8 release. A significant correlation between IL-8 release and the LLNA EC(3) was found (Pearson correlation r=0.743, p=0.0036, n=12). On the contrary, the activation of p38 MAPK showed no significant correlation between LLNA data and vigor of p38 MAPK activation. Overall, data presented confirm our previous observations and reveal IL-8 as potential tool not only to identify sensitizers, with the exception of pro-haptens, but also to classify them according to their potency, while p38 MAPK activation allows the identification of all sensitizers, including pro-haptens, but was not useful for potency classification.
PMID: 20541004

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