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G. Yang and Y. Huang
pro-inflammatory stimuli, chemical stress, environmental stress, and steroids [109,
110]. Elevated IL-8 levels lead to chronic inflammation, for instance, rheumatoid
arthritis, inflammatory bowel disease, and so on [111]. Therefore, many methods for
IL-8 signal transduction blocking have been employed to treat inflammatory diseases,
and two monoclonal IL-8 neutralizing antibodies (Abs), ABX-IL-8 and HuMab10F8,
have been developed, while the efficacy was unsatisfactory. Sung et al. [112] obtained
an IL-8 aptamer 8A-35 (K D = ∼1.72 pM) modified with 2
-fluorouracil, which
prevent IL-8 from binding to its receptor, thereby regulating IL-8-related intracellular
signal transduction pathways and chemotaxis. It is suggested that 8A-35 has the
potential for inflammatory diseases therapies.
6.4.1.5 Interleukin-10
Interleukin-10 (IL-10) is a critical inhibitor of inflammation caused by chronic
infection and cancer [113–115]. The power of the mice immune system to clear
viral infection or inhibit tumor growth can be reversed by antibody-mediated IL10 blocking [116]. Therefore, IL-10-mediated immunosuppression also performs
similar functions in human chronic infectious diseases or cancers [117]. In view of
the insufficiency of IL-10 blocking or antibody neutralizing agents, Berezhnoy et al.
[118] identified the IL-10 receptor (IL-10R) aptamer A1.2-4FL through 12 rounds
of SELEX, which specifically bound to the IL-10 receptor on the cell surface and
blocked the function of IL-10 in vitro. In the mice colon cancer CT26 tumor model,
the inhibitory effect of A1.2-4FL was equivalent of IL-10R neutralizing antibody
on tumor growth, suggesting that IL-10 blockade has great developing potential in
chronic infectious diseases and cancer therapeutics.
6.4.1.6 Interleukin-11
Interleukin-11 (IL-11) belongs to the IL-6 cytokines family, which is produced by
osteoblasts, synoviocytes, fibroblasts, and multiple types of cells in vitro [119].
Studies have indicated that IL-11 has pro-inflammatory and anti-inflammatory regulatory function as well as a variety of biological activities, including stimulating
acute phase response and inducing immunoglobulin production [120]. IL-11 interacts with receptors on macrophages to form a positive feedback autocrine loop and
exert its anti-inflammatory effect by directly inhibiting the release of inflammatory
factors such as TNF-α, IL-1b, and IL-12p40 [121]. Arap et al. [122] screened and
synthesized a polypeptide aptamer that mimics the specific ligand binding domain
of IL-11R α to CGRAGGSC, and evaluated the inhibitory efficiency of the aptamer
on the combination of IL-11 to IL-11R α in prostate cancer and skin tissues.
G. Yang and Y. Huang
pro-inflammatory stimuli, chemical stress, environmental stress, and steroids [109,
110]. Elevated IL-8 levels lead to chronic inflammation, for instance, rheumatoid
arthritis, inflammatory bowel disease, and so on [111]. Therefore, many methods for
IL-8 signal transduction blocking have been employed to treat inflammatory diseases,
and two monoclonal IL-8 neutralizing antibodies (Abs), ABX-IL-8 and HuMab10F8,
have been developed, while the efficacy was unsatisfactory. Sung et al. [112] obtained
an IL-8 aptamer 8A-35 (K D = ∼1.72 pM) modified with 2
-fluorouracil, which
prevent IL-8 from binding to its receptor, thereby regulating IL-8-related intracellular
signal transduction pathways and chemotaxis. It is suggested that 8A-35 has the
potential for inflammatory diseases therapies.
6.4.1.5 Interleukin-10
Interleukin-10 (IL-10) is a critical inhibitor of inflammation caused by chronic
infection and cancer [113–115]. The power of the mice immune system to clear
viral infection or inhibit tumor growth can be reversed by antibody-mediated IL10 blocking [116]. Therefore, IL-10-mediated immunosuppression also performs
similar functions in human chronic infectious diseases or cancers [117]. In view of
the insufficiency of IL-10 blocking or antibody neutralizing agents, Berezhnoy et al.
[118] identified the IL-10 receptor (IL-10R) aptamer A1.2-4FL through 12 rounds
of SELEX, which specifically bound to the IL-10 receptor on the cell surface and
blocked the function of IL-10 in vitro. In the mice colon cancer CT26 tumor model,
the inhibitory effect of A1.2-4FL was equivalent of IL-10R neutralizing antibody
on tumor growth, suggesting that IL-10 blockade has great developing potential in
chronic infectious diseases and cancer therapeutics.
6.4.1.6 Interleukin-11
Interleukin-11 (IL-11) belongs to the IL-6 cytokines family, which is produced by
osteoblasts, synoviocytes, fibroblasts, and multiple types of cells in vitro [119].
Studies have indicated that IL-11 has pro-inflammatory and anti-inflammatory regulatory function as well as a variety of biological activities, including stimulating
acute phase response and inducing immunoglobulin production [120]. IL-11 interacts with receptors on macrophages to form a positive feedback autocrine loop and
exert its anti-inflammatory effect by directly inhibiting the release of inflammatory
factors such as TNF-α, IL-1b, and IL-12p40 [121]. Arap et al. [122] screened and
synthesized a polypeptide aptamer that mimics the specific ligand binding domain
of IL-11R α to CGRAGGSC, and evaluated the inhibitory efficiency of the aptamer
on the combination of IL-11 to IL-11R α in prostate cancer and skin tissues.