LILRB2 controls inflammation induced by ANGPTL2 in synoviocytes

概要

ㄽ ᩥ ඲ ᩥ せ ⣙

LILRB2 controls inflammation induced
by ANGPTL2 in synoviocytes
㸦LILRB2 ࡣ⁥⭷⣽⬊࡟࠾࠸࡚
ANGPTL2 ࡟ࡼࡿ⅖⑕ࢆไᚚࡍࡿ㸧

୺ᣦᑟᩍဨ㸸㇂ᮏ ᖾኴ㑻ᩍᤵ
㸦་⣔⛉Ꮫ◊✲⛉ ṑ⛉▹ṇᏛ㸧
๪ᣦᑟᩍဨ㸸௣ծ ୍ᘯᩍᤵ
㸦་⣔⛉Ꮫ◊✲⛉ ඛ➃ṑ⛉⿵⥛Ꮫ㸧
๪ᣦᑟᩍဨ㸸ୖ⏣ ᏹ෸ᩍᤵ
㸦་⣔⛉Ꮫ◊✲⛉ ṑ⛉▹ṇᏛ㸧

すᒣ Ἃ⏤⌮
㸦་ṑ⸆ಖ೺Ꮫ◊✲⛉ ་ṑ⸆Ꮫᑓᨷ㸧

ኚᙧᛶ㢡㛵⠇⑕㸦TMJ-OA㸧ࡣୗ㢡㢌㌾㦵ࡢኚᛶ࣭◚ቯࢆ≉ᚩ࡜ࡍࡿ㏥⾜ᛶ⑓ኚ࡛࠶
ࡾ㐍⾜ࡍࡿ࡜㛤ည࡞࡝ࡢ୙ṇညྜࢆᘬࡁ㉳ࡇࡍ㞴἞ᛶ⑌ᝈ࡛࠶ࡿࠋTMJ-OA ࡢึᮇẁ㝵
࡛ࡣ⁥⭷⅖ࢆక࠺ࡇ࡜ࡀከࡃ, Ⓨ⑕࠾ࡼࡧ㐍⾜ࡢཎᅉࡢ୍ࡘ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋ⁥⭷⣽⬊ࡣ
ࢧ࢖ࢺ࢝࢖ࣥ࡞࡝ࡢ⅖⑕ㄏⓎᛶ࣓ࢹ࢕࢚࣮ࢱ࣮ࢆ㛵⠇⭍ෆ࡟ᨺฟࡋ, ᭱⤊ⓗ࡟ MMPs ࡜࠸
ࡗࡓᇶ㉁ศゎ㓝⣲ࢆ㐣๫࡟ㄏᑟࡍࡿࡇ࡜࡛㌾㦵ࡣ◚ቯࡉࢀࡿࠋ
࢔ࣥࢪ࣏࢚࢜ࢳࣥᵝᅉᏊ 㸦ANGPTL2㸧ࡣ⤌⧊ᦆയࡢಟ᚟ࡸࣜࣔࢹࣜࣥࢢ࡟㛵୚ࡋ࡚
࠾ࡾࡑࡢᶵ⬟ஹ㐍ࡣ៏ᛶ⅖⑕ࢆᘬࡁ㉳ࡇࡋᵝࠎ࡞⑌ᝈࡢⓎ⑕࣭ቑᝏ࡟㛵㐃ࡍࡿࡇ࡜ࡀ
᫂ࡽ࠿࡟࡞ࡗ࡚࠸ࡿࠋⓑ⾑⌫ච␿ࢢࣟࣈࣜࣥᵝཷᐜయ B2㸦LILRB2㸧ࡣ ANGPTL2 ࡢཷᐜ
య࡛࠶ࡿࡇ࡜ࡀ☜ㄆࡉࢀ, 㐀⾑ᖿ⣽⬊ࡢቑṪࡸ⒴ࡢⓎ⏕, 㐍⾜࡟㛵୚ࡋ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ
࠿࡜࡞ࡗࡓࠋࡋ࠿ࡋ࡞ࡀࡽ, ANGPTL2-LILRB2 axis ࡢ⁥⭷ࡢ⅖⑕࡬ࡢ㛵୚ࡣ୙࡛᫂࠶ࡿࠋ
ᮏ◊✲ࡣ, ⁥⭷⣽⬊࡟࠾ࡅࡿ LILRB2 ࢆ௓ࡋࡓ ANGPTL2 ࡢ⅖⑕㛵㐃ᅉᏊ࡬ࡢᙳ㡪ࢆゎ᫂
ࡍࡿ࡜࡜ࡶ࡟, JAK/STAT ࢩࢢࢼࣝ࡟ࡘ࠸࡚ࡶ᳨ウࢆຍ࠼ࡓࠋ
1. ࣄࢺ⭸㛵⠇⏤᮶⥺⥔ⱆ⣽⬊ᵝ⁥⭷⣽⬊㸦HFLS㸧࡟࠾ࡅࡿ࢖ࣥࢸࢢࣜࣥ α5, β1 ࠾ࡼࡧ
LILRB2 ࡢⓎ⌧ࢆ☜ㄆࡍࡿࡓࡵ, ᐃ㔞 PCR ࢆ⾜ࡗࡓࠋ
2. HFLS ࡟࠾࠸࡚ ANGPTL2 ࡀ⅖⑕㛵㐃ᅉᏊࡢ㑇ఏᏊⓎ⌧ࢆㄏᑟࡍࡿ࠿ྰ࠿ࢆ☜ㄆࡍࡿ
ࡓࡵ, ୖグཷᐜయ࠾ࡼࡧ⅖⑕㛵㐃ᅉᏊ㸦IL-1β, IL-6, TNF-α, COX-2, bFGF, MCSF,
MMP-3㸧ࡢ㑇ఏᏊⓎ⌧ࢆࣜ࢔ࣝࢱ࢖࣒ PCR ࡛ᐃ㔞ࡋࡓࠋࡲࡓ, MAPKs, NF-κB ࠾ࡼࡧ
Akt ࢩࢢࢼࣝ࡟ࡘ࠸࡚࢙࢘ࢫࢱࣥࣈࣟࢵࢺࢆ⏝࠸᳨࡚ウࡋࡓࠋ
3. HFLS ⣽⬊ࢆ⏝࠸, ANGPTL2 ㄏᑟᛶࡢ⅖⑕࡟ᑐࡍࡿ LILRB2 ࡢ㛵୚ࢆ᫂ࡽ࠿࡟ࡍࡿࡓ
ࡵ, LILRB2 ୰࿴ᢠయࢆ⏝࠸, ANGPTL2 ౫Ꮡᛶࡢ⅖⑕㛵㐃ᅉᏊࡢ㑇ఏᏊⓎ⌧࡬ࡢᙳ㡪
ࢆࣜ࢔ࣝࢱ࢖࣒ PCR ࡟ࡼࡗ࡚ゎᯒࡋࡓࠋࡲࡓ, MAPKs, NF-κB ࠾ࡼࡧ Akt ࡢࣜࣥ㓟໬
ࢆ࢙࢘ࢫࢱࣥࣈࣟࢵࢺゎᯒࢆ⏝࠸᳨ウࡋࡓࠋ
4. ANGPTL2 ㄏᑟᛶࡢ⅖⑕࡟ࡼࡿ JAK ࢩࢢࢼࣝఏ㐩⤒㊰࡬ࡢᙳ㡪ࢆ☜ㄆࡍࡿࡓࡵ, HFLS
࡟ ANGPTL2 ࠾ࡼࡧ LILRB2 ୰࿴ᢠయࢆῧຍࡋ, JAKs㸦JAK1, JAK2, JAK3 ࠾ࡼࡧ
Tyk2㸧ࡢࣜࣥ㓟໬࡟ཬࡰࡍᙳ㡪࡟ࡘ࠸࡚࢙࢘ࢫࢱࣥࣈࣟࢵࢺゎᯒࢆ⏝࠸᳨࡚ウࡋࡓࠋ
ࡇࢀࡽࡢᐇ㦂ࡼࡾ, ௨ୗࡢࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ
1. HFLS ࡟࠾࠸࡚࢖ࣥࢸࢢࣜࣥ α5, β1 ࠾ࡼࡧ LILRB2 ࡢ㑇ఏᏊⓎ⌧ࡀㄆࡵࡽࢀࡓࠋ
2. ANGPTL2 ࡣ࢖ࣥࢸࢢࣜࣥ α5, β1, LILRB2 ࠾ࡼࡧ࠸ࡎࢀࡢ⅖⑕㛵㐃ᅉᏊࡢ㑇ఏᏊⓎ⌧
ࣞ࣋ࣝࢆୖ᪼ࡉࡏࡓࠋࡲࡓ, MAPKs, NF-κB ࠾ࡼࡧ Akt ࡢࣜࣥ㓟໬ࢆஹ㐍ࡋࡓࠋ
3. LILRB2 ୰࿴ᢠయࡣ ANGPTL2 ౫Ꮡᛶࡢ⅖⑕㛵㐃ᅉᏊࡢ㑇ఏᏊⓎ⌧࡜, MAPK, NF-κB
࠾ࡼࡧ Akt ࡢࣜࣥ㓟໬ࢆᢚไࡋࡓࠋ
4. ANGPTL2 ࡣ JAK1, JAK2, JAK3 ࠾ࡼࡧ Tyk2 ࡢࣜࣥ㓟໬ࢆಁ㐍ࡋࡓࡀ, LILRB2 ୰࿴
ᢠయࡣ JAK1, JAK2, Tyk2 ࡢࣜࣥ㓟໬ࢆᢚไࡋࡓࠋ
௨ୖࡢ⤖ᯝ, ⁥⭷⣽⬊࡟࠾࠸࡚, ANGPTL2 ࡣ LILRB2 ࢆ௓ࡋ࡚ MAPKs, NF-κB, Akt,
JAK1, JAK2 ࠾ࡼࡧ Tyk2 ࡢࣜࣥ㓟໬ࢆಁ㐍ࡍࡿࡇ࡜࡟ࡼࡾ, ⅖⑕ࢆច㉳ࡍࡿྍ⬟ᛶࡀ♧၀
ࡉࢀࡓࠋ