Biomedical Engineering Reference
In-Depth Information
that is why it has been used widely for controlled drug delivery.
125-127
Its muco-
adhesive properties increase transcellular and paracellular transport across the
mucosal epithelium that potentially facilitates gene delivery to mucosa- and
bronchus-associated lymphoid tissue
128
making it an ideal agent for gene-
delivery agent for effective gene expression therapy.
73
cNPs have also been demonstrated as effective gene-delivery vehicles.
73
pDNAs were transported in cNPs and expressed in the lung epithelium of mice.
The results indicated that intranasal delivery of plasmids by with cNPs resulted
in sustained expression of the encoded protein in the lung which led to an effec-
tive supply of therapeutic or prophylactic levels of an immunomodulatory mol-
ecule. The group of Kong demonstrated treatment with chitosan interferon-γ
(IFN-γ) plasmid deoxyribonucleic acid (DNA) NPs (chitosan interferon-γ
nanogene [CIN or cIFN]) led to in situ production of IFN-γ and a reduction in
inflammation and airway reactivity in mice. Recently, the effect of cIFN treat-
ment on the immune responses of CD8
+
T cells and dendritic cells was exam-
ined in a BALB/c mouse model of ovalbumin (OVA)-induced allergic asthma.
Examination of dendritic cells from lung and lymph nodes indicated that cIFN
treatment decreased their antigen-presenting activity that was shown from the
lower CD80 and CD86 expression. In addition, the cIFN treatment reduced the
level of CD11c
+
b
+
dendritic cells in lymph nodes which possibly indicates that
endogenous IFN-γ expression may immunomodulate dendritic cell migration
and activation. The cIFN therapy resulted in the reduced levels of pro-inflam-
matory CD8
+
T cells and antigen-presenting activity of dendritic cells.
Interferon-γ (IFN-γ) has been extensively studied for immunomodulatory
and antiviral activity since its discovery.
73
Studies have shown that mice lacking
the IFN-γ receptor exhibit a T-helper (Th)2-like cytokine profile that suggests
that IFN-γ may play a role as a key cytokine in asthma.
129
IFN-γ delivers the
stimulatory signal for interleukin (IL)-12,
129
which induces the Th1 response
and inhibits Th2 cells by down-regulating the production of IL-4 and IL-5.
73
The interleukin IL-18 that induces IFN-γ also shifts the immune response from
a Th2 to a Th1 state.
130
The interferons, IFN-α, IFN-β, and IFN-γ, inhibit leu-
kotriene C
4
production in murine macrophages
131
while IFN-γ treatment of
guinea pigs released prostanoids and nitric oxide that affected the airway epi-
thelium that modified airway smooth muscle responses.
132
The production of
IFN-γ and IFN-γ-dependent IL-12 in whole blood cultures is lower in patients
with allergic asthma after stimulation with a mitogen.
133
As a result of the recip-
rocal regulation of T-helper cells, it was projected that IFN-γ level increases
with the use of IFN-γ in cNPs (chitosan interferon-γ nanogene [cIFN]) would
promote a Th1 response by blocking Th2 cytokine production.
73
Because the
IFN-γ upregulates the IL-13Rα2 decoy receptor this causes diminished IL-13
signaling
134
as well as decreased goblet cell hyperplasia and eosinophilia.
135
In
allergic individuals, IFN-γ inhibits the release of leukotrienes from peripheral
blood leukocytes (PBLs) after wasp venom immunotherapy.
136
IFN-γ performs
other functions that includes down-regulation of transforming growth factor β
