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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2015 ; 290
(11
): 7151-9
Nephropedia Template TP
Pasula R
; Azad AK
; Gardner JC
; Schlesinger LS
; McCormack FX
J Biol Chem
2015[Mar]; 290
(11
): 7151-9
PMID25605711
show ga
Augmentation of innate immune defenses is an appealing adjunctive strategy for
treatment of pulmonary Mycobacterium tuberculosis infections, especially those
caused by drug-resistant strains. The effect of intranasal administration of
keratinocyte growth factor (KGF), an epithelial mitogen and differentiation
factor, on M. tuberculosis infection in mice was tested in prophylaxis,
treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis
resulted in inoculum size-dependent weight loss and mortality. A single dose of
KGF given 1 day prior to infection with 10(5) M. tuberculosis bacilli prevented
weight loss and enhanced pulmonary mycobacterial clearance (compared with
saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was
delivered intranasally every third day for 15 days, but weight loss and bacillary
growth resumed when KGF was withdrawn. For mice with a well established M.
tuberculosis infection, KGF given every 3 days beginning on day 15
postinoculation was associated with reversal of weight loss and an increase in M.
tuberculosis clearance. In in vitro co-culture experiments, M.
tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated
alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent
killing through mechanisms that included promotion of phagolysosome fusion and
induction of nitric oxide. Alveolar macrophages from KGF-treated mice also
exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide
evidence that administration of KGF promotes M. tuberculosis clearance through
GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis
infection.
|Animals
[MESH]
|Antitubercular Agents/*therapeutic use
[MESH]
|Cells, Cultured
[MESH]
|Female
[MESH]
|Fibroblast Growth Factor 7/*therapeutic use
[MESH]