Biomedical Engineering Reference
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proteases that represent major regulators in skin desquamation. Further-
more, KLKs are upregulated in psoriasis, 38 a fact that may be linked to
upregulation of the IL-20 subfamily 17 in peeling-skin syndrome, 39 rosacea, 34
and atopic dermatitis. 40,41 In addition, high levels of LL-37 have been shown
in psoriasis and in rosacea. 34,35
9.1.2.3 Asthma
Plasma kallikrein and KLK1 are responsible for the generation of kinins as
described (Figure 9.1B). Whereas plasma kallikrein is mainly expressed in the
liver and circulates as a zymogen, it is KLK1 that is expressed in airways, where
it mediates bronchoconstriction, induction of mucus hypersecretion, and vas-
cular permeability, and triggers cholinergic and sensory nerve stimulation. 42-44
Bradykinin inhalation by normal volunteers and asthmatic patients 42 and in
animal models for asthma has been shown to cause immediate bronchocon-
striction, 45 as well as indicating a major role of KLK1 in asthma.
A
KALLIKREINS
K
K
P
s
(
)
Chromosome 19
Chromosome 4
locus organization
1 5
32 4
4
4
5
5
5 6
6
6
7
7
789 0 1 2 3 4
9 10 11 12
9 10 11 12
14
14
single gene
1
1
15
15
3
3
2
2
8
8
13
13
TGA
TGA
ATG
His
His
Asp
Asp
Ser
Ser
KLK gene structure
A
A
G
G
T
T
A
A
KLK protein
pre
pro
serine protease domain
B
Plasma
kallikrein
KLK1
aminopeptidase
LMWK
Lys-BK
BK
HMWK
carboxypeptidase
Des-Arg 9 -BK
B2 receptor
B1 receptor
Figure 9.1
Schematic representation of human kallikrein gene and protein structure.
(A) Structure of tissue and plasma kallikreins. (B) Crosstalk between
KLK1 and plasma kallikrein (KLKB1). BK, bradykinin; HMWK, high-
molecular-weight kininogen; LMWK, low-molecular-weight kininogen;
Lys-BK, lysine-bradykinin.
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